Bio-Rad Laboratories, Inc.v.Fluidigm Corporation

Patent Trial and Appeal Board

Apr 21, 2016

09953103 (P.T.A.B. Apr. 21, 2016)

Trials@uspto.gov Paper 32
571-272-7822 Entered: April 21, 2016
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

BIO-RAD LABORATORIES, INC.,
Petitioner,

v.

CALIFORNIA INSTITUTE OF TECHNOLOGY and
FLUIDIGM CORPORATION,
Patent Owner.
____________

Case IPR2015-00009
Patent 7,294,503 B2

Before GRACE KARAFFA OBERMANN, DONNA M. PRAISS, and
KRISTINA M. KALAN, Administrative Patent Judges.

PRAISS, Administrative Patent Judge.

FINAL WRITTEN DECISION
35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
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Bio-Rad Laboratories, Inc. (“Petitioner”) filed a Petition to institute an
inter partes review of claims 1, 2, 5–15, 18, 19, 30–35, 39–43, 46, 47, and
49–51 of U.S. Patent No. 7,294,503 B2 (Ex. 1001, “the ’503 patent”)
pursuant to 35 U.S.C. §§ 311–319, relying on the Declaration of Dr. Shelley
Anna (Ex. 1002, the “Anna Declaration”). Paper 1 (“Pet.”). The Board
granted the Petition and instituted trial for claims 1, 2, 5–11, 18, 19, 30, 31,
46, 47, and 49–51. Paper 16 (“Dec. on Inst.”). Trial was instituted on the
following grounds:
(1) Claims 1, 2, 5–11, 18, 19, 30, 31, 46, 47, and 49–51 as obvious
over Stewart II1 and Burns;2
(2) Claims 49 and 51 as obvious over Stewart II, Burns, and
Kobayashi;3 and
(3) Claims 18, 19, 46, and 47 as obvious over Stewart II, Burns, and
Chou.4
During trial, Patent Owner, California Institute of Technology and its
exclusive licensee Fluidigm Corporation (collectively, “Patent Owner”),
filed a Patent Owner Response relying on the Declaration of Dr. Todd
Squires (Ex. 2019, the “Squires Declaration”). Paper 21 (“PO Resp.”).
Petitioner filed a Reply to Patent Owner’s Response. Paper 23 (“Pet.

1 WO 84/02000, published May 24, 1984 (Ex. 1004).
2 WO 98/22625, published May 28, 1998 (Ex. 1005).
3 Kobayashi, et al., Production and Characterization of Monodispersed Oil-
in-Water Microspheres Using Microchannels, Food Sci. Technol. Res. 5(4),
350–55 (1999) (Ex. 1012).
4 Chou, et al., Microfabricated Devices for Sizing DNA and Sorting Cells,
Proceedings of the SPIE, Vol. 3258, 181–87 (1998) (Ex. 1006).
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Reply”). An unopposed Motion to Seal Exhibits 2003–2008 was filed by
Fluidigm Corporation. Paper 11.
A consolidated oral hearing was held on January 5, 2016, with
concurrently-filed inter partes review proceeding IPR2015-00010 involving
U.S. Patent No. 8,252,539, which issued from a continuation of the ’503
patent. A transcript of the hearing is included in the record. Paper 30
(“Tr.”).
We have jurisdiction under 35 U.S.C. § 6(c). This final written
decision is issued pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73.
For the reasons that follow, we determine that Petitioner has met its
burden to prove by a preponderance of the evidence that claims 1, 2, 5–15,
18, 19, 30–35, 39–43, 46, 47, and 49–51 of the ’503 patent are unpatentable.

I. BACKGROUND
A. The ’503 Patent (Ex. 1001)
The ’503 patent, titled “Microfabricated Crossflow Devices and
Methods,” is directed to a microfluidic device for analyzing and/or sorting
biological materials. Ex. 1001, Abstr. The device comprises a main
channel, through which a fluid incompatible with the biological material
flows, an inlet region in communication with the main channel, and a droplet
extrusion region, through which droplets of solution containing the
biological material are deposited into the main channel. Id. The droplet
extrusion region is “a junction between an inlet region and the main
channel” that “permits the introduction of a pressurized fluid to the main
channel at an angle perpendicular to the flow of fluid in the main channel.”
Id. at 13:28–32. Figures 16A and 16B are reproduced below.
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Figures 16A and 16B are exemplary architectures for droplet extrusion
regions in the microfabricated device. Id. at 7:60–61. The channels are
microfabricated, such as by etching a silicon chip. Id. at 17:29–33.
Channels that are rounded and have a diameter between about 2 and 100
microns are preferred for particles or molecules that are in droplets within
the main channel flow. Id. at 18:25–31. At these dimensions, the droplets
“tend to conform to the size and shape of the channels, while maintaining
their respective volumes.” Id. at 18:41–43. “[T]he size and frequency of
droplets formed in a main channel of such devices may be precisely
controlled by modifying the relative pressure of the incompatible fluids (e.g.,
water and oil) in the device.” Id. at 55:62–66. Modifying the relative
pressures produces water droplets in the oil stream “such that the water
enter[s] the droplet extrusion region, shearing off into discrete droplets.” Id.
at 56:52–56.

B. Illustrative Claim
Claims 1, 46, 49, and 50 are the independent claims at issue. Claim 1
is illustrative:
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1. A microfluidic product comprising:
(a) a main channel with a diameter of between about 2 and 100
microns or cross-sectional dimensions in the range of 1 to 100
microns in fluidic communication with a source of extrusion
fluid passing therethrough;
(b) a second microfluidic channel, wherein said channel has a
diameter in the range of 2 to 100 microns or cross-sectional
dimensions in the range of 1 to 100 microns and is in fluidic
communication with a source of sample fluid, and said sample
fluid is immiscible with the extrusion fluid; and
(c) said second microfluidic channel having at least one inlet
region in communication with the main channel in a droplet
extrusion region, the inlet region having a particle containing
sample fluid immiscible with the extrusion fluid passing
therethrough and constructed and arranged so that droplets of
the sample fluid are sheared into the main channel at the
extrusion region resulting in discrete sample fluid droplets
containing particles in the extrusion fluid stream.
Ex. 1001, 62:19–38. Claim 46 recites “a source of particle containing
sample fluid” and “the main channel resides in a layer of elastomeric
material.” Id. at 64:56–57, 64:63–64. Claim 49 recites “wherein
when the extrusion fluid is flowed through the first channel at a first
pressure and the sample fluid is flowed through the second channel at
a second pressure lower than the first pressure, monodisperse droplets
of aqueous solution are formed at the junction.” Id. at 66:1–5.
Claim 50 recites “an output channel in communication with the
junction.” Id. at 66:16.
C. Claim Interpretation
In an inter partes review, claim terms in an unexpired patent are
interpreted according to their “broadest reasonable construction in light of
the specification of the patent in which [they] appear[].” 37 C.F.R.
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§ 42.100(b). Under that standard, claim terms are given their ordinary and
customary meaning, as would be understood by one of ordinary skill in the
art in the context of the entire disclosure. In re Translogic Tech., Inc., 504
F.3d 1249, 1257 (Fed. Cir. 2007). Also, care is exercised to avoid reading a
particular embodiment appearing in the written description into the claim if
the claim language is broader than the embodiment. See In re Van Geuns,
988 F.2d 1181, 1184 (Fed. Cir. 1993) (“limitations are not to be read into the
claims from the specification”).
In our Decision on Institution, we interpreted two claim terms of the
’503 patent as shown below:
Table 1
Term Construction
sheared severed or broken off
monodisperse sample fluid droplets dispersed droplets of sample fluid of substantially uniform size

Dec. on Inst. 6–7. The parties do not challenge our claim constructions.
Consequently, for purposes of this Final Written Decision, we adopt the
constructions as stated in Table 1 in accordance with the analysis set forth in
our Decision on Institution. Id.

II. ANALYSIS
We turn now to the patentability of the claims. To prevail in its
challenges to the patentability of the claims, Petitioner must establish facts
supporting its challenges by a preponderance of the evidence. 35 U.S.C.
§ 316(e); 37 C.F.R. § 42.1(d). As noted above, there are three grounds of
unpatentability under 35 U.S.C. § 103(a) involved in this inter partes review
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proceeding: (1) claims 1, 2, 5–11, 18, 19, 30, 31, 46, 47, and 49–51 as
obvious over Stewart II and Burns; (2) claims 49 and 51 as obvious over
Stewart II, Burns, and Kobayashi; and (3) claims 18, 19, 46, and 47 as
obvious over Stewart II, Burns, and Chou.
We consider the respective positions of the parties in light of the
record before us.
A. Principles of Law
A claim is unpatentable under § 103(a) if the differences between the
claimed subject matter and the prior art are such that the subject matter, as a
whole, would have been obvious at the time the invention was made to a
person having ordinary skill in the art to which said subject matter pertains.
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007). The question of
obviousness is resolved on the basis of underlying factual determinations,
including: (1) the scope and content of the prior art; (2) any differences
between the claimed subject matter and the prior art; (3) the level of skill in
the art; and (4) where in evidence, so-called secondary conditions. See
Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966). We also recognize
that prior art references must be “considered together with the knowledge of
one of ordinary skill in the pertinent art.” In re Paulsen, 30 F.3d 1475, 1480
(Fed. Cir. 1994) (citing In re Samour, 571 F.2d 559, 562 (CCPA 1978)).

B. Level of Skill in the Art
In determining the level of skill in the art, various factors may be
considered, including “type of problems encountered in the art; prior art
solutions to those problems; rapidity with which innovations are made;
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sophistication of the technology; and educational level of active workers in
the field.” In re GPAC, Inc., 57 F.3d 1573, 1579 (Fed. Cir. 1995) (citing
Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962
(Fed. Cir. 1986)). There is evidence in the record before us that reflects the
knowledge level of a person with ordinary skill in the art. Petitioner’s
Declarant, Dr. Anna, attests that a person with ordinary skill in the art would
“hav[e] at least the equivalent of a Bachelor’s degree in engineering,
physics, or chemistry and two years of academic, research, or industry
experience related to fluid mechanics, fluid dynamics, or microfluidics.”
Ex. 1002 ¶ 29. Patent Owner does not dispute Dr. Anna’s assessment of the
level of ordinary skill. PO Resp. 3. Thus, we adopt Petitioner’s Declarant’s
attestation as to the level of skill in the art.
C. Overview of Stewart II
Stewart II describes a method and apparatus “particularly suited to the
manipulation of microscopic quantities of reactant with volumes of less than
10 nanolitres . . . .” Ex. 1004, 3. The reactants used in the system “can be
liquids” which “will be supported, defined and moved by another,
immiscible liquid, referred to hereafter as the carrier phase.” Id. at 4.
Figure 1, below, depicts two conduits for carrying out the method of
producing droplets of reactants as taught by Stewart II.
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Figure 1 illustrates one method of separating droplets of a predetermined
volume from a larger reservoir of reactant. Id. The stippled areas indicate
carrier phase (1) in one of the conduits. Id. at 2. The droplet volume shown
as (5) is pushed or sucked out of small opening (3) before separation of the
reactant from the side arm (2) into the carrier phase. A flow of carrier phase
separates the droplet and carries it down the conduit. Id. at 4. The
dimensions of the conduits are described by Stewart II as follows: “All
conduits should have diameters approximately the same as the droplets to be
used in them.” Id. at 5. The apparatus may be constructed by etching,
molding, or machining “indentations or channels of the appropriate
configuration in the surface of a plate, and [clamping or holding] this plate
against another, producing closed ducts or conduits.” Id. at 7. Suggested
materials for the plate include glass, Teflon, metal, polyvinylchloride, and
polypropylene with one of the plates being preferably transparent to allow
“visual inspection of the procedures.” Id.
Stewart II discloses three methods for determining the volume of the
droplet produced. Id. at 4–5. The second method, quoted below, uses two
currents to generate droplets of reactant in the apparatus described above:
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If large numbers of droplets are required, a continuous flow of
carrier phase flows down the conduit. When reactant is
simultaneously passed through the opening 3 a series of
droplets will be formed, each broken off just before it spans the
conduit. The exact size of the droplets thus produced will
depend on the magnitudes of the two currents.
Id. at 4–5. The droplets may contain micro-organisms. Id. at 7.
D. Overview of Burns
Burns relates to microfabricated substrates and methods for
amplifying and detecting nucleic acids. Ex. 1005, Abstract. Micromachined
structures for use with nanoliter volumes, called “microdevices,” are
preferred. Id. at 5:4–5. Materials such as silicon, quartz, and glass are
preferred because they can be manipulated to define channels, such as by
etching. Id. at 6:23–28. One or more channels in the substrate connect the
components, are preferably in liquid communication, and the channels
configured in microns accommodate “microdroplets.” Id. at 7:9–14.
Illustrative size ranges for the channels are 0.5 to 50 µm in depth and 20 to
1000 µm in width and, for the microdroplets, are “approximately 0.01 and
100 nanoliters (more typically between ten and fifty).” Id. at 7:15–19.
Figure 3B, below, is an embodiment of the device.

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Figure 3B shows “a schematic of . . . a device (10) to split a nanoliter-
volume liquid sample and move it using external air.” Id. at 50:17–18. Gas
is injected (lower arrow) “to split a microdroplet of length ‘L’.” Id. at
50:24–27. “[L]iquid . . . placed at the inlet (20) is drawn in by surface
forces.” Id. at 50:17–29. “[O]verflow ports (30) may be blocked or may be
loaded with excess water to increase the resistance to flow.” Id. at 50:28–
29. “[A] hydrophobic gas vent (70) further down the channel . . . can stop
the liquid microdroplet (60) after moving beyond the vent (70).” Id. at 51:1–
3.
E. Obviousness over Stewart II and Burns
Independent Claims 1, 46, 49, 51
Claim 1 recites “a main channel with a diameter of between about 2
and 100 microns or cross-sectional dimensions in the range of 1 to 100
microns.” Ex. 1001, 62:20–22. Claim 1 also recites “a second microfluidic
channel” with the same dimensions. Id. at 62:24–27. Petitioner argues that
the claimed dimensions for the microfluidic product’s channels are not
patentably distinct from Stewart II’s device because the claimed device
would not perform differently from the prior art device. Pet. at 19–20 (citing
Gardner v. TEC Syst., Inc., 725 F.2d 1338 (Fed. Cir. 1984)). Petitioner
provides the Anna Declaration as support for its contention that the forces
governing the behavior of fluid in a channel with Stewart II’s calculated
dimension of 267 microns in diameter are the same as those governing the
behavior of a fluid “in an otherwise similar channel with a diameter of 100
microns.” Id. at 20; Ex. 1002 ¶¶ 49–50. The basis for Dr. Anna’s opinion is
that the relative magnitudes of the capillary forces, viscous forces, and
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inertia governing droplet formation or breakup are similar in sub-millimeter
devices. Ex. 1002 ¶ 50.
Petitioner also asserts that “these particular dimensions are obvious in
light of Burns.” Pet. 19. According to Petitioner, “Burns specifically recites
that ‘illustrative ranges for channels [for microfluidic devices] may be
between 0.5 and 50/µm in depth (preferably between 5 and 20 µm) and
between 20 and 1000/µm in width (preferably 500/µm).’” Id. at 20 (citing
Ex. 1005, 7:16–19). Petitioner’s rationale for combining Stewart II and
Burns is based on the teaching in Stewart II to use channel sizes less than 10
nanoliters in volume, which Dr. Anna calculates to be a 267 micron
diameter. Id. at 8 (citing Ex. 1002 ¶¶ 41–42), 20. As discussed above,
Petitioner argues that “the forces governing the behavior of fluid in a
channel with a diameter of 267 microns, as disclosed in Stewart II, would be
the same as those governing the behavior of fluid in an otherwise similar
channel with a diameter of 100 microns.” Id. at 20 (citing Ex. 1002 ¶¶ 49–
50). Therefore, one of ordinary skill in the art, in determining an appropriate
channel size for the Stewart II device, would have included the channel
dimensions described by Burns and would have understood the use of
channel sizes in the range of 1–100 microns both (1) was technically
possible and (2) could have been predictably and effectively used in a
droplet-creating device as taught by Stewart II. Id. at 20–21.
Claim 1 further requires that the second microfluidic channel have “at
least one inlet region in communication with the main channel” and that the
inlet region be “constructed and arranged so that droplets of the sample fluid
are sheared into the main channel”. Ex. 1001, 62:30–36. Petitioner asserts
that Stewart II discloses “a droplet-creating device” in which channel sizes
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of 1–100 microns could be effectively and predictably used in view of
Burns. Pet. 21 (citing Ex. 1002 ¶ 66).
Petitioner also asserts that Burns and Stewart II disclose properties of
the fluids recited in claims 1 (particle containing sample fluid), 46 (particle
containing sample fluid), 49 (first pressure and second pressure), and 51
(first pressure and second pressure), even though these limitations should not
be given patentable weight. Id. at 22–25. Likewise, Petitioner argues that
the “monodisperse droplets” recited in claims 49 and 51 are merely
properties of the sample and extrusion fluids, but, nevertheless, obvious
from the teaching in Stewart II that large numbers of droplets can be formed
from passing reactant into a continuous flow of carrier, that the conduits
have diameters approximately the same as the droplets to be used in them,
and that optimization to produce monodisperse droplets with regular
periodicity in Stewart II’s device would have been within the level of
ordinary skill in the art. Id. at 26 (citing Ex. 1004, 5; Ex. 1002 ¶¶ 34, 76–
79). According to Dr. Anna, one of ordinary skill in the art would have
known how to optimize Stewart II’s device by varying the pressures of the
carrier phase and reactant to form monodisperse droplets. Ex. 1002 ¶¶ 77–
78 (providing Kawakatsu5 (Ex. 1011) and Kobayashi (Ex. 1012) as
examples of monodisperse droplets being achieved by optimizing devices
without undue experimentation).
Petitioner also argues that the recitations in claims 49 and 51 of “a
diameter less than 60 microns” for the droplet size are merely properties of

5 Kawakatsu et al., Effect of Microchannel Structure on Droplet Size During
Crossflow Microchannel Emulsification, J. Surfactants and Detergents, Vol.
3, No. 3 (July 2000).
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the fluids, which nevertheless would have been obvious over Stewart II’s
teaching of droplet diameters in view of Burns’s teaching of microdevice
diameters. See id. at 27–28. The additional requirement of claim 46 that the
main channel reside in a layer of elastomeric material would have been an
obvious substitution of materials in view of Stewart II’s disclosure of
channels residing in a polymer block that is adjacent to one or more
substrates, according to Petitioner. Id. at 32 (citing Ex. 1004, 7, 8; Ex. 1002
¶¶ 83–85).
Patent Owner contends that the Anna Declaration should be given
little weight because Dr. Anna has taken inconsistent positions and her
explanations are not credible. PO Resp. 4–9. Dr. Anna testified at
deposition that “Thorsen [a named inventor on the ’503 patent and author of
a 2001 article (Ex. 2017)] was the first to publish generating droplets at a
microfluidic T-junction.” PO Resp. 6–8 (citing Ex. 2018, 62:8–63:21).
According to Patent Owner, Dr. Anna’s deposition testimony is consistent
with statements attributed to her in a 2007 journal article (Ex. 2016), that
Patent Owner quotes as follows:
3.2 Droplet breakup in cross-flowing streams
One of the most common microfluidic methods of generating
droplets uses cross-flowing continuous and dispersed phase
streams. In microfluidics, this is typically implemented using T-
shaped microchannel junctions, depicted schematically in figure
1(b). Droplet formation in a T-shaped device was first reported
by Thorsen et al [53], who used pressure controlled flow in
microchannels 35μm wide and 6.5μm deep to generate droplets
of water in a variety of different oils.
Id. at 5 (quoting Ex. 2016, R322). Patent Owner contends the statements in
the article “were made well after the work of Stewart and Burns had
published” and independent of this proceeding, but are inconsistent with her
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positions regarding Stewart II, Burns, and the ’503 patent in this proceeding.
Id. at 5–6.
Patent Owner contends that Dr. Anna’s explanation that Stewart II
“would not have been considered part of the popular microfluidics field that
we think of that I was referring to in this review article” is inconsistent with
her declaration statement that “Stewart II falls squarely within the definition
of microfluidics.” Id. at 7–8 (quoting Ex. 2018, 62:8–63:21, citing Ex. 1002
¶ 42). Patent Owner also contends that the 2007 article contains no
qualifiers to support Dr. Anna’s testimony that the article pertained to a
particular time period. Id. at 8.
Patent Owner further contends that Dr. Anna’s Declaration should be
given little weight because she “was unable to answer basic questions about
the understanding a person of ordinary skill in the art would have regarding
the disclosure of the prior art.” Id. at 9–10. Patent Owner specifically
asserts a “lack of ability to answer question[s] on how . . . a reduction in
channel [size] would affect the operation of the Stewart II device” and on the
“cost of materials as those relate to the materials disclosed in Stewart II.”
Id. at 11. Patent Owner further asserts that “Dr. Anna was asked if
Kobayashi forms droplets using a cross-flow” and was unable to answer the
question other than by reading from her declaration statement. Id. at 12–13.
Patent Owner also asserts that the combination of Burns with Stewart
II is improper because (1) Burns teaches away from Stewart II and (2) the
combination is unpredictable and lacks a reasonable chance of success. Id.
at 28–42. Patent Owner argues that “having the ‘microdroplet’ remain in
contact with the channel walls is expressly discouraged by Stewart II”
because Stewart II maintains a film of the continuous phase around the
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reactant to reduce or eliminate contamination of the reactant while Burns’s
channels contact the dispersed phase and, therefore, are incompatible with
forming a spherical droplet. Patent Owner also argues that the smaller
dimensions of Burns’s channels “would increase the possibility of an
obstruction, protrusion, or imperfection on the wall from contacting the
dispersed phase.” Id. at 28–31, 37 (citing Ex. 2019 ¶¶ 39–42).
Regarding predictability, Patent Owner contends that has not been
demonstrated because Dr. Anna’s declaration states that the teachings of the
references are compatible with each other, not that their combination yields
a predictable result. Id. at 32–33. Additionally, Dr. Anna’s deposition
testimony regarding needing more factors in order to predict how changing
one variable would affect Stewart II’s system evidences unpredictability,
according to Patent Owner. Id. at 33 (citing Ex. 2018, 110:12–13, 111:17–
19, 112:10–12, 114:3–8). Patent Owner asserts that “the factors involved in
droplet formation are numerous and complex,” would not have been known
well enough to predictably be manipulated at the time of the invention of the
’503 patent, and the prior art does not “provide[] guidance on what
combinations would succeed.” Id. at 33–36 (citing Ex. 2019 ¶¶ 23–27, 29,
30, 37, 38). Patent Owner also asserts that “implausible and inconsistent
statements within Stewart II” would “cause skepticism” about successful
droplet formation and evidence unreliability of the Stewart II disclosure. Id.
at 38–40. Specifically, Patent Owner asserts that Stewart II’s claim that the
T-junction can generate droplets at volumes from more than 1 liter to less
than 10 nL is “impossible under any reasonable operating parameters.” Id.
at 38 (citing Ex. 2019 ¶ 35). Patent Owner also asserts that Stewart II’s
disclosure of generating a large amount of droplets using a continuous flow
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of carrier phase is inconsistent with both the statement that “the present
invention does not operate a continuous stream” and Stewart II’s method of
combining droplets for chemical reactions “using a sequence of distinct and
discrete steps.” Id. at 38–39 (citing Ex. 2019 ¶¶ 47–48). Patent Owner
further argues that the second channel or side arm of Stewart II would not
necessarily have the same dimension as the main channel because the side
arm does not also contain droplets. Id. at 45–47.
Patent Owner presents generally the same arguments regarding the
patentability of independent claims 1, 46, 49, and 51, but presents additional
arguments directed to the elastomeric material required by claim 46 and the
monodispersity required by claims 49 and 51. Patent Owner contends that
“the Petition does not provide any rationale [] why one of ordinary skill in
the art would use an elastomer in light of the teachings of Stewart II alone.
Nor does the Petition allege that Burns cures this deficiency.” Id. at 50.
Patent Owner also contends that “there is a structural element in the claims
that must be constructed to form monodisperse droplets having a diameter of
less than 60 microns” as specified in claim 51. Id. at 53. Patent Owner
asserts that this is not disclosed in Stewart II and that Dr. Anna’s assertion
that monodispersity can be achieved in a microfluidic channel by optimizing
pressure is not supported by Kobayashi. Id. at 54–57.

Dependent Claims 2, 5–11, 18, 19, 30, 31, 47, and 50
Claims 2, 5, and 7 depend from claim 1 and require that the extrusion
fluid is a non-polar solvent, the sample solution is aqueous, and the particles
are biological material, respectively. Ex. 1001, 62:30–40, 62:46–47, 62:51–
52. Claim 6 further defines the aqueous solution of claim 5. Id. at 62:48–
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50. Claims 8–11 further define the biological material of claim 7. Id. at
62:53–63. Claims 30 and 31 depend from claim 1 and further define the
extrusion fluid in terms of its refractive index. Id. at 63:49–53. Petitioner
argues that the dependent claims are obvious over Stewart II and Burns
because the fluids and properties of the fluids do not distinguish the claimed
apparatus patentably over the prior art. Pet. 28, 30 (citing id. at 8–9).
Nevertheless, Petitioner argues that the use of a TE buffer (Tris-HCl and
EDTA) in a sample solution and the modification of the sample
concentration as taught by Burns makes obvious the buffer composition of
claim 6, and the selection of a viral particle as the biological material meets
the requirements of claims 8, 9, and 11. Id. at 28–31.
Regarding the elastomeric material recited in claims 18, 19, and 47, as
discussed with respect to claim 46 above, Petitioner argues the limitations
would be an obvious substitution of materials in view of Stewart II’s
disclosure of channels residing in a polymer block that is adjacent to one or
more substrates. Id. at 32 (citing Ex. 1004, 7, 8; Ex. 1002 ¶¶ 83–85).
Patent Owner does not separately argue the patentability of dependent
claims 2, 5–11, 30, and 31. Regarding the elastomeric material of claims 18,
19, and 47, Patent Owner argues that the Petition lacks a rationale for the
substitution, and that the deficiency of Stewart II is not cured by Burns. PO
Resp. 50.

Discussion
At the outset, we note that Patent Owner contends that the testimony
of Dr. Anna should be given little weight, but does not seek to exclude the
Anna Declaration. Patent Owner does not challenge Dr. Anna’s
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qualifications as an expert in the field of microfluidics. Tr. 28:16–18.
Instead, Patent Owner argues that the credibility of her statements regarding
Stewart II is diminished by her cross-examination at deposition on the
subject of (a) her paper, independent of this proceeding, that acknowledges
the Thorsen 2001 Article and (b) hypotheticals concerning the Stewart II
device presented at deposition. PO Resp. 4–14.
Patent Owner essentially contends that Dr. Anna’s deposition and
declaration statements in this proceeding concerning Stewart II are
inconsistent with statements in her earlier publication indicating that the
named inventors on the ’503 patent were the first to report droplet formation
in a T-shaped device. Dr. Anna explained she was unaware of Stewart II at
the time of her publication and that, even in view of Stewart II, her
published statements about the Thorsen 2001 Article being the first to report
on microdroplet formation in a T-shaped device would still be accurate,
because Stewart II was not part of the body of work reported in the academic
literature. Ex. 2018, 31:9–11, 59:21–60:3, 61:2–12, 63:11–21. The veracity
of Dr. Anna’s explanation is supported by Patent Owner’s expert, Dr.
Squires, who testified at deposition that he does not typically include patents
in his own academic review papers and did not cite the patent literature in
his own papers on the subject of microfluidics. Ex. 1020, 31:5–9, 37:19–
38:21, 40:20–41:17. Dr. Anna’s deposition testimony, in fact, clarifies any
apparent inconsistency between her declaration and the Thorson 2001
Article. Accordingly, we are not persuaded that Dr. Anna’s testimony
should be given diminished weight in light of her prior statements about the
Thorson 2001 Article.
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Regarding hypothetical modifications to the Stewart II device that Dr.
Anna allegedly could not answer during deposition, Patent Owner asserts
Dr. Anna was “asked to discuss the effect that reducing the channel size
would have on Stewart II’s device.” PO Resp. 10–11 (citing Ex. 2018,
113:4–115:5, 109:24–110:13). Patent Owner’s questions, however, were
hypotheticals concerning contamination or pressure, which, Dr. Anna
testified, required additional information about the nature of the
contamination. Ex. 2018, 113:4–6, 113:11–14, 114:9–12. Patent Owner
further asserts that Dr. Anna was not able to explain “how one of ordinary
skill in the art would understand the dimensions and operation of SII’s
device in light of the disclosure it works at both 10nl and 1L volumes.” PO
Resp. 10 (citing Ex. 2018, 107:21–109:16). That assertion is unpersuasive,
because the questions presented to Dr. Anna were directed to the forces that
govern droplet formation at 10nl and 1L; Dr. Anna testified that the relevant
forces were the same, specifically, viscous forces, capillary forces, and
inertia. Ex. 2018, 107:21–108:2, 108:10–19.
Patent Owner further asserts that Dr. Anna’s credibility is undermined
by her inability to opine on “low material costs” mentioned in Chou or
whether “Kobayashi forms droplets using a cross-flow.” PO Resp. 11–13
(citing Ex. 2018, 142:18–145:6, 137:2–140:4). The cost of materials asked
about at deposition, however, went beyond the scope of Dr. Anna’s
declaration, as Dr. Anna’s declaration does not address relative material
costs. Dr. Anna did opine at deposition that materials mentioned in Stewart
II may be cheaper than those in Chou depending on additional factors.
Ex. 2018, 142:18–145:6. As to Kobayashi, Dr. Anna testified that
“Kobayashi uses microchannels with pressure-driven flow to form
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monodisperse droplets, as does Stewart” (Ex. 2018, 140:22–24) and
“[w]hether a pressure-driven flow is the same as a cross-flow depends on the
context.” Ex. 2018, 139, 17–19. We do not find Dr. Anna’s deposition
testimony to undermine the credibility of her declaration in this proceeding
because the questions asked of the witness were fairly answered. Therefore,
after considering arguments and evidence by both Petitioner and Patent
Owner, we are not persuaded that Dr. Anna’s testimony is entitled to little or
no weight.
Regarding Petitioner’s prior art challenges, there is no dispute that the
10 nanoliter volume disclosed in Stewart II translates to a 267 micron
diameter in the size of a spherical droplet in the channel. Ex. 1002 ¶ 42; Ex.
1020, 149:15–150:10. There also is no dispute that Stewart II discloses a
microfluidic device having two channels arranged so that droplets of a
sample fluid in the second channel are capable of being sheared into the
main channel containing an extrusion fluid. Ex. 1002 ¶¶ 45–48, 50–57; Ex.
1020, 163:17–168:16. The key issue is whether the disclosure in Burns of a
particular channel size (between 5 and 20 microns in depth) and a specific
material (elastomeric) for microfluidic devices is properly combined with
the disclosures of Stewart II.
We are persuaded that Petitioner meets its burden of showing that the
selection of known channel sizes for microfluidic devices as disclosed in
Burns would have been obvious as a predictable variation in the same field
because the dimensions of Burns are less than 267 microns as directed by
Stewart II. KSR, 550 U.S. at 417. The combination is supported by the
Anna Declaration. Dr. Anna testified that the fluid behavior in the Stewart II
device would be “substantially the same” in a device having the dimensions
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disclosed by Burns. Ex. 1002 ¶ 50 (“fluid behavior (including flow
characteristics, fluid forces, etc.) would be substantially the same in devices
designed for droplets of less than 267 microns as they would be in devices
designed for droplets of less than 100 microns.”). Dr. Squires’s testimony
that the combination of Burns with Stewart II would have been
unpredictable with no reasonable expectation of success due to multiple
factors affecting droplet formation is not supported by the record. See Ex.
2019 ¶¶ 23–27, 29, 30, 37, 38. Dr. Squires’s opinion is based on Stewart II
being unbelievable because it does not disclose operating data. Id. at ¶¶ 29–
30. Referring to Burns, Dr. Squires further states “[n]or does the mere fact
that channels with dimensions smaller than 100 microns could be fabricated
at the time of invention provide a basis for one of ordinary skill in the art to
believe that Stewart II’s device would operate as described by Stewart II
when using channels with dimensions of 100 microns or less.” Id. at ¶ 37.
The formation of microdroplets, however, is disclosed in both Stewart II and
Burns. Stewart II discloses droplet formation in a microfluidic device at
dimensions less than 267 microns in diameter. Ex. 1004, 3–4. Burns
discloses droplet formation in a microfluidic device at the claimed
dimensions. Ex. 1005, 7. While multiple factors may affect droplet
formation, the formation of droplets in devices having a channel that is less
than 267 microns in diameter (Stewart II) or in the claimed range (Burns) is
supported by the evidence.
Dr. Squires’s testimony regarding the combination of Stewart II and
Burns is based also on his assertion that the 10nL size disclosed in Stewart II
would not be accepted by one of ordinary skill in the art at the time of the
invention because “the upper bound volume in Stewart II is so implausible.”
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Ex. 2019 ¶ 36. However, Dr. Squires admitted at deposition that it was
“physically possible” to make one liter droplets using Stewart II’s device
under low gravity and pressure conditions, such as in outer space. Ex. 1020,
176:21–177:6. Stewart II states that some types of chemical analysis or
synthesis can be conducted in its device in space. Ex. 1004, 8 (“It could also
be used for chemical analysis or synthesis in outer space, in conditions of
very low gravity and pressure.”). Stewart II also discloses a continuous flow
embodiment having two currents that form a series of droplets when a
reactant passes through an opening such that each droplet is “broken off just
before it spans the conduit” and that “[a]ll conduits should have diameters
approximately the same as the droplets.” Id. at 4, 5. In a determination of
obviousness, a reference may be relied upon for all that it would have
reasonably suggested to one having ordinary skill in the art. Merck & Co. v.
Biocraft Labs., 874 F.2d 804, 807 (Fed. Cir. 1989) (“That the [prior art]
patent discloses a multitude of effective combinations does not render any
particular formulation less obvious.”).
Dr. Squires asserts that “one of ordinary skill in the art would have to
perform his or her own independent experimentation and research to
determine what operating parameters could be combined to form a droplet
using the T-junction geometry disclosed by Stewart II.” Ex. 2019 ¶ 30.
Such experimentation has not been shown on this record to be undue
experimentation. In addition to the formation of microdroplets in the
devices of Stewart II and Burns, the evidence shows, as Dr. Squires
concedes, that for given materials, dimensions, and geometries, it would be a
matter of “simple optimization” to adjust pressure to form droplets and is
relatively easy to do. Ex. 1020, 134:12–135:5. Therefore, in view of the
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totality of the evidence in the record, we credit Dr. Anna’s testimony on the
combination of Stewart II and Burns to arrive at the microfluidic product as
claimed in claim 1.
We are not persuaded that Burns teaches away from the asserted
combination as argued by Patent Owner. See PO Resp. 28. “A reference
may be said to teach away when a person of ordinary skill, upon reading the
reference, would be discouraged from following the path set out in the
reference, or would be led in a direction divergent from the path that was
taken by the applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
According to Patent Owner, the operation of Burns’s system, showing a
droplet in contact with a channel wall, is incompatible with Stewart II in two
ways: (1) Stewart II requires a continuous phase between the channel and
the dispersed phase to reduce contamination by the reactants in the dispersed
phase, and (2) Stewart II requires droplets to be spherical. PO Resp. 29–30.
These distinctions between the two references do not amount to
discouraging one skilled in the art from the path leading to the claimed
invention. Both Burns and Stewart II address contamination of the walls and
disclose ways in which to reduce contamination, including making the walls
smooth and washing them. Ex. 1005, 108; Ex. 1004, 2, 7. The common
objective of Burns and Stewart II would have provided a further reason to
combine their disclosures, rather than discouraging the combination. In
addition, the evidence does not support a particular droplet geometry being
critical to the microfluidic device of Stewart II as asserted by Patent Owner.
See PO Resp. 30. Dr. Squires testified that the droplets shown in Figure 1 of
Stewart could have alternate shapes. Ex. 1020, 143:11–13.
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Regarding claims 18, 19, 46, and 47, Patent Owner also argues that
the Petition lacks a rationale for the substitution of elastomeric material for
the polymeric material in the device of Stewart II and that the Petition does
not argue the deficiency of Stewart II is cured by Burns. PO Resp. 48–50.
The Petition states that “Stewart discloses a number of alternative polymers
in which channels can be formed, and polymers include numerous
elastomeric materials.” Pet. 32 (citing Ex. 1002 ¶¶ 83–85). Petitioner
argues that the substitution of an elastomeric material would have been
prima facie obvious because it was known to be a suitable substitute for
other polymers in the field of microfluidics. Id. at 32–33 (citing Ex. 1002
¶ 85). According to Dr. Anna, such a substitution would have been
technically simple and would have yielded predictable results. Ex. 1002
¶ 85. Dr. Anna’s testimony on the subject is not refuted. Dr. Squires’s
assertion that swelling of the elastomeric material may occur in the presence
of “certain fluids” is not applicable to the combination of Stewart II and
Burns because Stewart II uses mineral oil as the carrier phase, which is the
same carrier phase fluid taught in the ’503 patent. Ex. 2019 ¶¶ 54–57; Ex.
1004, 4; Ex. 1001, 4:39–43. Based on the full trial record, the substitution of
an elastomeric material for the polymeric material in the device of Stewart II
would have been obvious as a predictable variation in the field of
microfluidic devices, and, therefore, Petitioner has met its burden in showing
that claims 18, 19, 46, and 47 would have been obvious over the
combination of Stewart II and Burns. See KSR, 550 U.S. at 417 (“If a person
of ordinary skill can implement a predictable variation, §103 likely bars its
patentability.”).
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Regarding the obviousness challenge as to claims 2, 5, 7, 10, 30, and
31, based on the combination of Stewart II and Burns, these claims all
depend directly or indirectly from claim 1 and recite limitations of the
properties of the sample and/or extrusion fluids. Ex. 1001, 62:39–63:53.
The Petition explicitly challenges claim 1 as obvious over the combination
of Stewart II and Burns and sets forth Petitioner’s obviousness grounds with
respect to each of the limitations recited in claim 1, including the limitations
that refer to properties of the fluid. Pet. 19–23. The Petition also argues that
the properties of the fluids do not impart patentable weight to the claims,
referencing Section VI.A.1.i. on pages 8–9 of the Petition, where this
argument is first expressed in connection with the challenge based on
anticipation by Stewart II. Id. at 22; see also id. at 23, 26, 28, 30.
Petitioner’s argument that the presence and properties of the sample and
extrusion fluids do not confer patentable weight to the claims identifies all
the claims to which this argument applies, namely, claims 1, 2, 5–11, 30, 31,
46, 49, and 41 [sic 51]. We agree with Petitioner that properties of the fluids
flowing through the claimed device impart no patentable weight to
dependent claims 2, 5, 7, 30, and 31. Catalina Marketing Int’l., Inc. v.
Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002) (“the
patentability of apparatus or composition claims depends on the claimed
structure, not on the use or purpose of the structure”) (citing In re Gardiner,
171 F.3d 313, 315–16 (CCPA 1948)).
In addition to the contentions above, Patent Owner argues that
objective indicia (secondary considerations) establish non-obviousness of
the claimed subject matter. PO Resp. 15–16. We analyze Patent Owner’s
proffered evidence in this regard in Section II.H. below.
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F. Obviousness over Stewart II, Burns, and Kobayashi
Petitioner asserts that if the combination of Stewart II and Burns
would not have rendered obvious the production of monodisperse droplets,
as required by claims 49 and 51, then the combination in further view of
Kobayashi would have rendered obvious the claimed microfluidic product.
Pet. 36–37. According to Petitioner, Kobayashi discloses forming
monodisperse oil-in-water emulsions in microchannels by adjusting
parameters such as pressure and concentration of surfactant. Id. (citing Ex.
1012; Ex. 1002 ¶¶ 97–99). Petitioner argues that Kobayashi evidences the
desire to achieve monodispersity of droplets in the microfluidic field and
that monodispersity can be achieved through optimization of a microfluidic
device. Id.
Patent Owner contends that Kobayashi creates droplets without
requiring a junction of channels and that the “size of droplets was
independent of adjustment of pressure beyond the pressure needed to create
a microsphere in the first place.” PO Resp. 57–58 (citing Ex. 1012, 353).
Because the manner in which droplets are formed in Kobayashi is different
from Stewart II, Patent Owner contends that “one of ordinary skill in the art
would not have considered [Kobayashi’s] method of forming monodisperse
microspheres to be helpful in modifying Stewart II to form monodisperse
droplets.” Id. at 58 (citing Ex. 2019 ¶ 59). Because size is not adjusted by
pressure beyond a certain point and only 10% of the channels produce
microspheres, Patent Owner contends that generating monodisperse
microspheres using Kobayashi’s system is neither routine optimization nor
simple. Id. at 58 (citing Ex. 2019 ¶¶ 60–62).
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We are persuaded that monodispersity of the droplets formed in a
microfluidic device is a property of the fluids contained in the device rather
than an element of the claimed structure of two channels with a junction, as
evidenced by Kobayashi itself. See Ex. 1020, 61:5–8 (Dr. Squires testified
that Kobayashi forms monodispersed oil-in-water droplets using
microchannels). Additionally, we find that Petitioner has met its burden to
show that it would have been within the skill of one of ordinary skill in the
art to optimize pressure and surface tension in order to form monodisperse
droplets. Ex. 1002 ¶ 77; Ex. 1012, 352. The difficulties noted by
Kobayashi, and argued by Patent Owner, were at higher surfactant
concentration, but at less than 0.5 percent weight; Dr. Squires testified that
Kobayashi’s “monodispersity was high.” Ex. 1020, 83:2–84:11. Therefore,
Petitioner has shown that monodispersity of droplets in microfluidic
channels as required by claims 49 and 51 was known and subject to pressure
and surface tension conditions.
G. Obviousness over Stewart II, Burns, Chou
Petitioner challenges claims 18, 19, 46, and 47 as obvious over the
combination of Stewart II, Burns, and Chou. Petitioner asserts that Chou
“specifically teaches forming channels in an elastomeric material adjacent to
a substrate layer,” with citations to the claim chart. Pet. 38. Petitioner
further asserts that it would have been obvious to substitute the elastomeric
material of Chou for the polymeric material taught by Stewart II because it
would have been technically simple and would have yielded predictable
results. Id. (citing Ex. 1002 ¶¶ 100, 101). The Anna Declaration supports
the known use of elastomeric materials in microfluidic devices, the ease of
substituting the material of Chou in the device of Stewart II, and the benefit
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of low material costs and an easy one-step process when silicone elastomer
is used to form the channel. Ex. 1002 ¶¶ 100, 101.
Patent Owner contends that if the elastomer in Chou is not cheaper
than the polymeric material in Stewart II, then there is no reason for the
asserted substitution. PO Resp. 51. Patent Owner further argues that such
substitution would not produce predictable results because the elastomer in
Chou “could swell and prevent [] formation of droplets in a variety of non-
aqueous fluids.” Id. (citing Ex. 2019 ¶ 57). We are not persuaded by Patent
Owner’s argument because there is no evidence in the record that the carrier
fluid of Stewart II would have been incompatible with the elastomer of
Chou. The carrier fluid of Stewart II is the same carrier fluid used in the
’503 patent. Ex. 1004, 4; Ex. 1001, 4:39–43.
We are persuaded that a known elastomeric polymer used to form a
channel in a microfluidic device would have been an obvious substitution of
material in Stewart II, and that the obviousness of interchanging them does
not depend on a price differential. See KSR, 550 U.S. at 417. Stewart II
teaches polymeric material generally with its recitation of an expansive list
of alternative polymers “Kel-F . . . polyvinylchloride, polypropylene etc.” as
the material in which a channel may be produced to form a conduit against a
second plate. Ex. 1004, 7. Chou’s disclosure of silicone elastomer to form
microfluidic channels supports Stewart II’s broad teaching of useful
polymeric materials. Ex. 1002 ¶¶ 83–85, 100; Pet. 32–33, and 37–38.
H. Objective Indicia of Non-Obviousness
In addition to the contentions above, Patent Owner argues that
objective indicia, including industry praise (PO Resp. 16–25) and long-felt
but unmet need (id. at 25–28) is probative evidence showing the inventions
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of the claims at issue are non-obvious. Id. at 16. In support, Patent Owner
relies on the Squires Declaration (Ex. 2019), the Anna Declaration (Ex.
1002), the Anna 2007 Article (Ex. 2016), and other evidence (Exs. 1007,
2018, 2021–25, 2027.
Industry Praise
Patent Owner contends that “the Thorsen 2001 Article is substantially
similar to Example 12 in the ’503 patent” and provides a chart setting forth
how the Thorsen 2001 Article (Ex. 2017) discloses the elements of claim 1.
PO Resp. 20–23. Patent Owner also sets forth how researchers in the field,
including Dr. Anna, praised the Thorsen 2001 Article as (1) first reporting
“droplet formation in a T-shaped device” (Ex. 2016), (2) “first introduc[ing
microfluidic T-junction geometry] for the controlled formation of water-in-
oil dispersions” (Ex. 2022), (3) “first incorporate[ing T-junction geometry]
into a microfluidic chip” (Ex. 2023), (4) “first[] consider[ing] droplet
formation within a T-junction microchannel” (Ex. 2024), and (5) “first
report[ing] “[d]roplet formation in a T-shaped device” (Ex. 2025). PO Resp.
16–19. It is not sufficient, however, that a product or its use merely falls
within the scope of a claim in order for objective evidence of
nonobviousness tied to that product to be given substantial weight. There
must also be a causal relationship, termed a “nexus,” between the evidence
and the claimed invention. Merck & Co., Inc. v. Teva Pharm. USA, Inc., 395
F.3d 1364, 1376 (Fed. Cir. 2005). Nexus must exist in relation to all types
of objective evidence of nonobviousness. See In re GPAC, Inc., 57 F.3d
1573, 1580 (Fed. Cir. 1995) (generally); Ormco Corp. v. Align Tech., Inc.,
463 F.3d 1299, 1312 (Fed. Cir. 2006) (long-felt but unmet need);
Muniauction, Inc. v. Thomson Corp., 532 F.3d 1318, 1328 (Fed. Cir. 2008)
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(praise). A showing of sufficient nexus is required in order to establish that
the evidence relied upon traces its basis to a novel element in the claim, not
to something in the prior art. Institut Pasteur & Universite Pierre Et Marie
Curie v. Focarino, 738 F.3d 1337, 1347 (Fed. Cir. 2013). Objective
evidence that results from something that is not “both claimed and novel in
the claim” lacks a nexus to the merits of the invention. In re Kao, 639 F.3d
1057, 1068 (Fed. Cir. 2011). Thus, establishing nexus involves a showing
that novel elements in the claim, not prior-art elements, account for the
objective evidence of nonobviousness. Id. The stronger the showing of
nexus, the more weight will be accorded the objective evidence of
nonobviousness. See GPAC, 57 F.3d at 1580 (“To the extent that the
patentee demonstrates the required nexus, his objective evidence of
nonobviousness will be accorded more or less weight.”); Ashland Oil, Inc. v.
Delta Resins & Refractories, Inc., 776 F.2d 281, 306 (Fed. Cir. 1985) (“The
objective evidence of secondary considerations may in any given case be
entitled to more or less weight, depending upon its nature and its relationship
to the merits of the invention.”).
As noted, the objective evidence cited by Patent Owner requires a
nexus with the claimed subject matter. Patent Owner’s evidence of praise
relies, however, on Thorsen being first to report on a T-shaped junction
geometry for a microfluidic device to produce droplets and, more generally,
to “landmark work” in droplet based microfluidics, not any specific praise
for the device itself even if encompassed by claim 1. See PO Resp. 17–19;
Ex. 2016, R322; Ex. 2021, 25; Ex. 2022, 142–44; Ex. 2023, 438; Ex. 2024,
712; Ex. 2025, 2036. As discussed above, T-shaped junctions were known
in the art for use in microfluidic devices as early as 1984. Ex. 1004, Fig. 1.
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Consequently, it cannot be used to tie the objective evidence of praise to the
claimed subject matter. Thus, even if being recognized as first to report in
the academic literature on a particular microfluidic structure constitutes
praise for the device, we are not persuaded that Patent Owner establishes
sufficient nexus in relation to the microfluidic device being praised versus
what is “both claimed and novel in the claim.” Kao, 639 F.3d at 1068.
Accordingly, we are not persuaded by Patent Owner’s contentions in relation
to praise in the industry.
Long-Felt but Unmet Need
Patent Owner also contends that long-felt need is established by the
length of time between Stewart II’s disclosure of a T-junction structure in
1984, Manz’s disclosure of capillary tubing having internal diameters
between 0.9 µm and 24 µm in 1990, and the earliest priority date of the ’503
patent in November 8, 2000. PO Resp. 25–28 (citing Leo Pharmaceutical
Prods., Ltd. v. Rea, 726 F.3d 1346, 1357–59 (Fed. Cir. 2013)).
Patent Owner’s evidence of a long-felt but unmet need is premised on
the prior art T-junction structure to form droplets of Stewart II not meeting
the need for miniaturization of microfluidic devices. See PO Resp. 25–26.
When asked about direct evidence of long-felt need at oral hearing, Patent
Owner answered, “Dr. Anna’s statement that Stewart II professed a desire to
reduce the size of his device.” Tr. 54:1–3. Patent Owner essentially takes
Petitioner’s reason to combine references and characterizes it as a “desire”
or “need” rather than a direction to use devices that are smaller than 267
microns in size. Patent Owner then measures the length of time between
Stewart II’s publication in 1984 and the November 8, 2000 filing date of the
’503 patent to argue an analogous situation to the finding of long-felt need in
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Leo Pharma. PO Resp. 26–27. The problem with this argument is that
Stewart II does not evidence difficulty in constructing a T-junction
microfluidic device in dimensions below 267 microns. Rather, Stewart II
discloses “the manipulation of microscopic quantities of reactant with
volumes of less than 10 nanolitres,” which the parties do not dispute
translates to droplets of less than 267 microns and channels of less than 267
microns in diameter. Ex. 1004, 3; Ex. 1002 ¶¶ 42, 44 (“Because Stewart II
expressly states that it is suited for volumes of less than 10 nanoliters, or less
than 267 microns, Stewart II expressly relates to smaller droplets as well . . .
.”); Ex. 1020, 149:19–150:10, 158:2–9 (When Stewart II says “ten nanoliters
or less” and spherical droplets are involved, this translates into a channel
width of “267 microns or less.”). Therefore, we are not persuaded that the
evidence on the complete record establishes a long-felt, unmet need for
microfluidic channels in the claimed range of 2 to 100 microns.
We also are not persuaded that the time gap drawn between
Stewart II’s 1984 publication and the ’503 patent priority date is sufficient to
establish long-felt need in view of the fourteen year gap in Leo Pharma, 726
F.3d at 1359. PO Resp. 27–28. Leo Pharma involved “the need for a single
formulation to treat psoriasis” where benefits of the separate components,
vitamin D and corticosteroids, were known from the cited prior art
references twenty-two years and fourteen years before the filing of the patent
at issue. Leo Pharma, 726 F.3d at 1359. The factual background of Leo
Pharma includes evidence that “several medical research articles . . .
discourag[ed] the combination of a vitamin D analog with a corticosteroid
because of the stability problems of vitamin D analogs at lower pHs.” Id. at
1353. There was also a finding that the cited prior art formulations were not
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storage stable and the problem of storage stability was not recognized. Id. at
1354, 1357. Thus, Leo Pharma included circumstances that are not present
here, not just the mere passage of time. See Nike, Inc. v. Adidas AG, 812
F.3d 1326, 1338 (Fed. Cir. 2016) (the decision in Leo Pharma “hinged on
the fact that nothing in the cited prior art appreciated the problem the
invention recognized and then solved” not merely the passage of time); Iron
Grip Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1325 (Fed. Cir.
2004) (“the mere passage of time without the claimed invention is not
evidence of nonobviousness.”). Even if the time span between cited prior art
and the priority date of a patent were sufficient to establish long-felt need,
Patent Owner has not addressed the Burns reference, published two years
prior to the ’503 patent priority date and relied upon by Petitioner in each of
its obviousness challenges. Ex. 1005. The evidence is insufficient to
establish that any long-felt need was solved by the invention of the ’503
patent, as opposed to the prior art techniques reflected in Burns.
Consequently, we are not persuaded by Patent Owner’s contentions with
respect to long-felt need.
I. Conclusion
After considering Petitioner’s and Patent Owner’s positions, as well as
their supporting evidence, we determine the preponderance of the evidence
demonstrates that (1) claims 1, 2, 5–11, 18, 19, 30, 31, 46, 47, and 49–51 of
the ’503 patent would have been obvious over Stewart II and Burns; (2)
claims 49 and 51 would have been obvious over Stewart II, Burns, and
Kobayashi; and (3) claims 18, 19, 46, and 47 would have been obvious over
Stewart II, Burns, and Chou for the reasons provided by Petitioner. See Pet.
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19–33, 36–60; Pet. Reply 1–25. Patent Owner’s objective evidence is not
sufficient to overcome the strong showing of obviousness in this case.
J. Motion to Seal
Fluidigm Corporation’s Motion to Seal Exhibits 2003–2008 (Paper
11) is unopposed and is granted. There is an expectation that information
will be made public where the information is identified in a final written
decision, and that confidential information that is subject to a protective
order ordinarily becomes public 45 days after final judgment in a trial,
unless a motion to expunge is granted. 37 C.F.R. § 42.56; Office Patent
Trial Practice Guide, 77 Fed. Reg. 48,756, 48,761 (Aug. 14, 2012). In
rendering this Final Written Decision, it was not necessary to identify, nor
discuss in detail, any confidential information because it was not relied upon
by the parties in their trial briefing. However, a party who is dissatisfied
with this Final Written Decision may appeal the Decision pursuant to 35
U.S.C. § 141(c), and has 63 days after the date of this Decision to file a
notice of appeal. 37 C.F.R. § 90.3(a). Thus, it remains necessary to maintain
the record, as is, until resolution of an appeal, if any. In view of the
foregoing, the confidential documents filed in the instant proceeding will
remain under seal, at least until the time period for filing a notice of appeal
has expired or, if an appeal is taken, the appeal process has concluded. The
record for the instant proceeding will be preserved in its entirety, and the
confidential documents will not be expunged or made public, pending
appeal. Notwithstanding 37 C.F.R. § 42.56 and the Office Patent Trial
Practice Guide, neither a motion to expunge confidential documents nor a
motion to maintain these documents under seal is necessary or authorized at
this time. See 37 C.F.R. § 42.5(b).
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36

This is a final written decision of the Board under 35 U.S.C. § 318(a).
Parties to the proceeding seeking judicial review of this decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.
III. ORDER
Accordingly, it is hereby:
ORDERED that, as set forth in Section II.I above, claims 1, 2, 5–11,
18, 19, 30, 31, 46, 47, and 49–51 of the ’503 patent have been shown to be
unpatentable.
FURTHER ORDERED that the Motion to Seal Exhibits 2003–2008
(Paper 11) is granted.
FURTHER ORDERED that the parties to the proceeding seeking
judicial review of this Final Written Decision must comply with the notice
and service requirements of 37 C.F.R. § 90.2.
.

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37

PETITIONER:

Dion Bregman
Michael Lyons
MORGAN LEWIS & BOCKIUS LLP
dbregman@morganlewis.com
mlyons@morganlewis.com

PATENT OWNER:

James P. Murphy
Margaux A. Savee
POLSINELLI PC
jpmurphy@polsinelli.com
msavee@polsinelli.com