us to. ov
`Trials
`Tel: 571-272-7822
`
`Paper 18
`.
`Entered: June 15, 2018, 2018
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`10X GENOIVHCS, INC.,
`
`Petitioner,
`
`V.
`
`BIO-RAD LABORATORIES, INC,
`Patent Owner.
`
`Case IPR2018-00301
`
`Patent 9,216,392 B2
`
`Before KRISTINA M. KALAN, JON B. TORNQUIST, and
`JEFFREY W. ABRAHAM, Administrative Patent Judges.
`
`TORNQUIST, Administrative Patent Judge.
`
`DECISION
`
`Denying Institution of Inter Partes Review
`35 USC. § 314(a)
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`1.
`
`INTRODUCTION
`
`10X Genomics, Inc. (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
`
`requesting inter partes review of claims 1—21 of US. Patent
`
`No. 9,216,392 B2 (Ex. 1001, “the ’392 patent”). Bio-Rad Laboratories, Inc.
`
`(“Patent Owner”) filed a Preliminary Response to the Petition (Paper 12,
`
`“Prelim. Resp”).1
`
`We have authority to determine whether to institute an inter partes
`
`review. 35 U.S.C. § 314. The standard for instituting an inter partes review
`
`is set forth in 35 U.S.C. § 314(a), which provides that an inter partes review
`
`may not be instituted “unless the Director determines .
`
`.
`
`. there is a
`
`reasonable likelihood that the petitioner would prevail with respect to at
`
`least 1 of the claims challenged in the petition.”
`
`After considering the Petition, the Preliminary Response, and the
`
`evidence of record, we determine that Petitioner has not demonstrated a
`
`reasonable likelihood that it would prevail with respect to at least one claim
`
`challenged in the Petition. Accordingly, we do not institute an inter partes
`
`review.
`
`1. Related Proceedings
`
`The parties identify Bio-Rad Laboratories, Inc. v. 10X Genomics, Inc,
`
`Case No. 3:17~CV-4339 (N.D. Cal.) and Re: Certain Microfluidic Devices,
`
`Investigation Number 337-TA-1068 (ITC) as related matters. Pet. 1; Paper
`
`5, 1. The parties also note that the ’392 patent is at issue in IPR2018-00300
`
`and IPR2018-00302. Pet. 1; Paper 7, 1.
`
`1 Patent Owner identifies Lawrence Livermore National Security LLC as a
`real party in interest. Paper 5, 1.
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`3. The ’392 Patent
`
`The ’392 patent discloses a system for forming an array of emulsions
`
`that consist of liquid droplets disposed in an immiscible carrier liquid.
`
`Ex. 1001, 1:46—47, 10:11—12. Figure 24, reproduced below, is a schematic
`
`’ View of a “four-port” droplet generator of the ’392 patent (id. at 35:41—42):
`
`Fig. 24
`
`
`
`In the droplet generator depicted in Figure 24, oil wells 1224 are loaded with
`
`a carrier fluid (e.g., oil) and sample well 1226 is loaded with a sample (e.g.,
`
`an assay mixture, such as a PCR mixture including a sample and a reagent).
`
`Id. at 35:42—47. The wells are “connected fluidly by channels 1230 formed
`
`near the bottom” of the well. Id. at 35:35—37. The individual channels
`
`connect at intersection 1232, where droplets are formed by “any suitable
`
`mechanism, such as flow—focusing.” Id. at 35:37—40. The ’392 patent
`
`explains that pressure may be applied to wells 1224 and 1226, as indicated
`
`by vertical arrows 1234, “to drive fluid flow, droplet generation, and flow of
`
`the resulting droplets as an emulsion 1236 to emulsion well 1228.” Id. at
`
`35:47—51.
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`Figures 22, 23, and 25 of the ’392'patent are reproduced below:
`
`PRESSURE
`SOURCE
`
`1234\
`
`
`12'30
`1230
`1250 1252 123012“4 12'42
`
`Figures 22 and 23 show exemplary device 1220 equipped with an array of
`
`droplet generators 1222. Id. at 35:27—30. As shown in Figure 23, each
`
`droplet generator 1222 may include wells, or reservoirs 1224, 1226, and
`
`1228, which can be accessed from above plate 1220. Id. at 35:32—35. The
`
`wells are fluidly connected by channels 1230. Id. at 35:35—40. Figure 25 is
`
`a section view of plate 1220 assembled with pressure manifold 1238, which
`
`is connected to one or more pressure sources (e.g., pressure sources 1248
`
`and 1250) that exert pressure on the oil and sample wells to drive fluid flow.
`
`Id. at 35:47—51, 35:56—59, 36:20—22, 36:36—41.
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`C. Illustrative Claim
`
`Petitioner challenges claims 1—21 of the ’392 patent. Claim 1, the
`
`only independent claim in the ’392 patent, is illustrative of the challenged
`
`claims and is reproduced below:
`
`1. A system for forming an array of emulsions, comprising:
`
`a plate including an array of emulsion production units, each
`unit including
`
`at least one first input well to hold a continuous phase for an
`emulsion,
`
`a second input well to hold a dispersed phase for an emulsion,
`and
`
`an output well connected to the first and second input wells by
`a set of channels that form a channel junction, the set of
`channels including at least two input channels extending
`separately from the input wells to the channel junction and an
`output channel extending from the channel junction to the
`output well, each channel of the set of channels being
`, circumferentially bounded; and
`
`a vacuum or pressure source configured to be connected
`operatively to wells of the plate to form a pressure drop
`between the input wells and the output well of each unit to
`drive the continuous phase and the dispersed phase from the
`first and second input wells of the unit to the channel junction,
`at which droplets of the dispersed phase are generated, and
`through the output channel for collection in the output well of
`the unit.
`
`Ex. 1001, 162:10—32.
`
`'J‘I
`
`

`

`IPR2018—00301
`
`Patent 9,216,392 B2
`
`D. The Asserted Grounds of Unpatentability
`Petitioner contends claims 1—21 of the ’392 patent are unpatentable
`
`based on the following grounds (Pet. 13, 52, 54, 57, 69):2
`
`References
`
`Basis
`
`Claim 3 Challen_ed
`
`Quake3, Dale“, Chien I5, and Chien H6
`
`§ 103
`
`1—6, 8, 10, 11, and 21
`
`Quake, Dale, Chien I, Chien II, and
`
`§ 103
`
`7
`
`Quake, Dale, Chien I, Chien II, and
`Modlin8
`
`§ 103
`
`
`Hsieh7
`
`Quake, Dale, Chien I, Chien II, and
`Soane9
`
`§ 103
`
`12—17, 19, and 20
`
`Quake, Dale, Chien I, Chien II, and
`Beer10
`
`§ 103
`
`18
`
`A. Claim Construction
`
`II.
`
`ANALYSIS
`
`In an inter partes review, claim terms in an unexpired patent are
`
`construed according to their broadest reaswiable interpretation in light of the
`
`2 Petitioner also relies on a declaration from Dr. Khushroo Gandhi
`
`(Ex. 1003).
`3 US 2002/0058332 A1, published May 16, 2002 (Ex. 1004).
`4 US 2008/0056948 A1, published Mar. 6, 2008 (Ex. 1005).
`5 US 6,915,679 B2, issued July 12, 2005 (Ex. 1006).
`6 Ring-Ling Chien and J. Wallace Parce, Multiportflow-control system for
`lab—on-a-chip microfluidic devices, Fresenius J. Anal. Chem. 371:106—1 11
`(2001) (Ex. 1035).
`7 US 2008/0166720 A1, published July 10, 2008 (Ex. 1019).
`8 US 2005/0266582 A1, published Dec. 1, 2005 (Ex. 1007).
`9 US 6,176,962 B1, issued Jan. 23, 2001 (BX. 102]).
`10 Beer et al., On-Chip, Real—Time, Single-Copy Polymerase Chain Reaction
`in Picoliter Droplets; Anal. Chem., 79, 8471—8475 (2007) (Ex. 1032).
`
`6
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`specification of the patent in which they appear. 37 CPR. § 42.100(b);
`
`Cuozzo Speed Techs, LLC v. Lee, 136 S. Ct. 2131, 2144—46 (2016)
`
`(upholding the use of the broadest reasonable interpretation standard).
`
`Upon review of the parties’ arguments and supporting evidence, we
`
`determine that no claim terms of the ’3 92 patent require express construction
`
`for purposes of this decision. See Nidec Motor Corp. v. Zhongshan Broad
`
`Ocean Motor Co., 868 F.3d 1013, 1017 (Fed. Cir. 2017) (citing Vivid Techs,
`
`Inc'. v. Am. Sci. & Eng ’g, Inc, 200 F.3d 795, 803 (Fed. Cir. 1999) (“[O]nly
`
`those terms need be construed that are in controversy, and only to the extent
`
`necessary to resolve the controversy.”)).
`
`B. Claims 1-6, 8, 10, 11, and 21 over Quake, Dale, Chien I, and
`Chien 1]
`
`Petitioner contends the subject matter of claims 1—6, 8, 10, 11, and 21
`
`would have been obvious over the combined disclosures of Quake, Dale,
`
`Chien I, and Chien 11. Pet. 13—5 1.
`
`1. Quake
`
`Quake discloses a device and methods for analyzing and/or sorting
`
`biological materials, including, proteins, enzymes, viruses, and cells.
`
`Ex. 1004, Abstract. The devices and methods of Quake comprise “at least
`one analysis unit having an inlet region in communication with a main ’
`
`channel at a droplet extrusion region (e.g., for introducing droplets of sample
`
`into the main channel),” a detection region, and a detector associated with
`
`the detection region. Id. 11 76. As the droplets pass into the detection region,
`
`they are examined by the detector for a predetermined charactcristic. Id.
`
`11 78. Quake teaches that some embodiments may include multiple detection
`
`regions and detectors, as well as “a discrimination region or branch point in
`
`

`

`IPR2018-00301
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`Patent 9,216,392 B2
`
`communication with the main channel and with branch channels, and a flow
`
`control responsive to the detector” for sorting droplets. Id. 111] 77, 79 (noting
`
`that a “plurality of analysis units of the invention may be combined in one
`
`device,” and that such a multiplexed system “can be adapted to provide a
`
`very high throughput”). Quake further discloses the option of using “a
`
`plurality of inlet regions, each of which introduces droplets of a different
`
`sample .
`
`.
`
`. into the main channel.” Id. 11 77.
`
`Quake’s droplet extrusion regions “are designed to compartmentalize
`
`small droplets of aqueous solution within microfluidic channels filled with
`
`oil.” Id. fl 3. Specifically, Quake explains
`
`[t]he droplet extrusion region generally comprises a junction
`- between the sample inlet and the main channel such that a
`pressurized solution of a sample (Le, a fluid containing a sample
`such as cells, Virions or molecules) is introduced to the main
`channel in droplets. Preferably, the sample inlet intersects the
`main channel such that
`the pressurized sample solution is
`introduced into the main channel at an angle perpendicular to a
`stream of fluid passing through the main channel. For example,
`in preferred embodiments,
`the sample inlet and main channel
`intercept at a T-shapedjunction; i.e., such that the sample inlet is
`perpendicular (90 degrees) to the main channel.
`
`Id. 11 84.
`
`Figure 16B of Quake, reproduced below, shows an exemplary
`
`architecture for droplet extrusion regions in a microfabricated device. Id.
`
`11 39.
`
`

`

`IPR2018—00301
`
`Patent 9,216,392 B2
`
`-~ 1603
`
`/1606
`
`FIG. 16B
`
`1605
`
`In Figure 16B, inlet channel 1603 intersects main channel 1605, forming a
`
`T-shaped junction. Id. 1111 15, 299—300. As an aqueous solution is
`
`pneumatically driven through channel 1603 it is sheared into droplets as it
`
`enters the oil stream in main channel 1605. Id. 1111 290, 299—300. These
`
`droplets then are driven through outlet channel 1604, and may subsequently
`
`be routed through different channel architectures to allow individual droplets
`
`to be sorted and/or analyzed. Id. 1111 16, 290, 294, 300.
`
`Quake explains that, in this process of droplet generation, the required
`
`fluids may be loaded into the microfabricated device via separate syringes
`
`that are fitted with high-pressure connection fittings. Id. 11 288. “The
`
`pressures of the different fluids are then adjusted so that their pressures are
`
`balanced at the droplet extrusion region.” Id. 11 290. “Droplet extrusion can
`
`then be initiated by slightly adjusting the pressure difference between the
`
`different fluids” so that the droplet fluid is sheared off at a fixed frequency.
`Id. Quake explains that this frequency of droplet generation “can be readily
`
`adjusted by simply adjusting the pressures of the individual fluid lines.” Id.
`
`2. Dale
`
`Dale discloses a vessel for performing microfluidic assays and, in
`
`particular, an “assembly for performing microfluidic assays [that] includes a
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`micro-fluidic chip with access ports,” microchannels that are in
`
`communication with the access ports, and a fluid cartridge that is configured
`
`to be coupled with one or more access ports. Ex. 1005, Abstract.
`
`Figure 1b of Dale is reproduced below:
`
`
`
`FlG. 1b
`
`As shown in Figure 1b, cartridge 10 is coupled to micro-fluidic chip 40. Id.
`
`11 28. Cartridge 10 may have internal chambers containing various fluids
`
`that are coupled to access ports 44, 46, and 48 of microfluidic chip 40 via
`
`nozzles 14, 16, and 18 (not numbered in Figure 1b). Id. 111] 29, 32—33.
`
`Microchannels extending through microchip 40 are in communication with
`
`access ports 44, 46, and 48. Id. 11 32. Cartridge 10 may include vacuum
`
`port 24 connected to a source of negative pressure (i.e., vacuum), and
`
`facilitates movement of reaction waste products into a waste chamber. Id.
`
`'n 29.
`
`3. Chien I
`
`Chien I discloses devices, systems, and methods for flexibly and
`
`selectively transporting “fluids within microfluidic channels of a
`
`microfluidic network by applying, controlling, and varying pressures at a
`
`plurality of reservoirs or ports.” Ex. 1006, 2:56—61. Figure 1 of Chien I is
`
`reproduced below:
`
`10
`
`

`

`IPR2018-00301
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`Patent 9,216,392 B2
`
`
`
`25‘.
`
`Fig. 1
`
`As shown in Figure 1, microfluidic system 10 includes microfluidic
`
`device 12 coupled to a bank of pressure modulators 14. Id. at 9:43—46.
`
`Each pressure modulator is in fluid communication with reservoir 18 of
`
`microfluidic device 12 via associated tube 20. Id. at 9:51—52.
`
`Figure 2 of Chien I, reproduced below, shows microfluidic device 12
`
`(id. at 10:35):
`
`
`
`Fig. 2
`
`Microfluidic device 12 includes an array of reservoirs 18a, 18b, etc. coupled
`
`together by microscale channels defining microfluidic network 30. Id.
`
`at 10:36—38. Chien I explains that the micrufluidic devices of the invention
`
`typically include at least one microscale channel and usually “at least two
`
`intersecting microscale channel segments” disposed within a single body
`
`structure. 1d. at 10:57—61.
`
`11
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`4. Chien II
`
`Chien 11 describes the same embodiment as Chien 1. Pet. 19. Chien H
`
`notes that, although hydrodynamic flow has been used in microfluidic
`
`systems, its use may have certain limitations:
`
`The use of external pumps to force liquids directly through
`microfluidic
`channels
`has
`previously
`been
`proposed.
`Incorporation of mechanical micro pumps and valves within a
`microfluidic device to move the fluids within a microfluidic
`
`channel has also been tested. Unfortunately, the flow rate in the
`microfluidic systems is usually on the order of nL s“. Accurate
`control of such a tiny flow of an incompressible liquid is
`extremely difficult. Lack of proper control of small pressure
`differences will yield irreproducible and erratic results. A system
`that controls the pressure of a compressible gas at the fluid-air
`interface directly on top of the wells of the microfluidic device is
`a more practical design.
`
`Ex. 1035, 106.
`
`5. Analysis
`
`Petitioner contends one of ordinary skill in the art would have found it
`
`obvious to combine the teachings of Quake, Dale, Chien I, and Chien II11 to
`
`form a “Combined System” that includes every limitation of independent
`
`claim 1. Pet. 14, 22, 27—42. The Combined System, as depicted by
`
`Petitioner, is reproduced below:
`
`” We refer to Chien I and Chien H collectively as “Chien.”
`
`l2
`
`

`

`IPR2018-00301
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`Patent 9,216,392 B2
`
`
`
`FIG. 1
`
`,Id. at 22.
`
`To form this Combined System, Petitioner contends an ordinary
`
`artisan would have first implemented multiple instances of Quake’s droplet
`
`generator on a single chip, such as the one disclosed in Dale, as depicted
`
`below:
`
`
`
`FIG 1613
`
`.7am»
`
`Id. at 18—19 (“Quake taken in View of Dale renders obvious the provision of
`
`multiple droplet generators on a single microfluidic chip, for multiple
`
`reasons”). Once a skilled artisan chose to implement multiple copies of
`
`Quake’s droplet generator on a single chip, Petitioner contends this skilled
`
`artisan would have found it obvious to use Chien’s pneumatic manifold and
`
`plate design to drive fluids through this parallelized array of droplet
`
`generators. Id. at 21—22.
`
`13
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`Petitioner contends one of ordinary skill in the art would have sought
`
`to combine Quake and Dale because parallelization was known to result in
`
`higher throughput, the proposed combination would enable multiplexing of
`
`different reactions, and implementation of Dale’s parallelization method
`
`would constitute the use of a known technique to improve a similar device in
`
`the same way. Id. at 18—19. Petitioner fiirther contends that one of ordinary
`
`skill in the art would have sought to implement Chien’s multi-reservoir plate
`
`and pressure control system in the Combined System because Chien’s
`
`system provides increased pressure control and would allow the omission of
`
`expensive fluid reservoirs and pumps. Id. at 25—26.
`
`Patent Owner argues Petitioner has failed to provide a reasonable
`
`explanation as to why one of ordinary skill in the art would have sought to
`
`combine Quake, Dale, and Chien. Prelim. Resp. 28—30. Patent Owner
`
`asserts Petitioner does not explain why a person of ordinary skill in the art
`
`would have taken “just a portion” of Quake’s device and then attempted “to
`
`replicate solely that portion in parallel in the single-layered chips of Dale,”
`
`or why Chien would have motivated one of ordinary skill in the art to
`
`modify Quake to incorporate its fluid drive technique. Id. at 28—29.
`
`Upon review of the parties’ arguments and supporting evidence, as
`
`well as Dr. Gandhi’s declaration testimony, we determine that Petitioner has
`
`not sufficiently demonstrated that one of ordinary skill in the art would have
`
`combined Quake, Dale, and Chien to arrive at the subject matter of the
`
`challenged claims.
`
`a. The Proposed Combination is not Clearly Defined
`
`As a preliminary matter, we find the proposed combination of Quake,
`
`Dale, and Chien is not clearly defined. Petitioner asserts that it would have
`
`14
`
`

`

`IPR2018-00301
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`Patent 9,216,392 B2
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`been “obvious that multiple instances of Quake’s droplet generator should
`
`be disposed on a single chip,” as depicted in the figures from Quake and
`
`Dale. Pet. 19 (emphases omitted); Ex. 1003 ‘H 66 (“Thus, in my view it was
`
`obvious that multiples of Quake’s emulsion generating units could be
`
`arranged on a single plate or chip as shown below .
`
`.
`
`. .”). From this
`
`statement, it appears that Petitioner proposes to parallelize only Quake’s
`
`droplet generators on a single chip. Indeed, this is the combination of
`
`elements Patent Owner addresses and criticizes in the Preliminary Response.
`
`Prelim. Resp. 28 (“Why would a POSA take just a portion of the multi-
`
`layered Quake device and attempt to replicate solely that portion in parallel
`
`in the single-layered chips of Dale?”).
`
`Other portions of the Petition, however, appear to contemplate
`
`incorporating the entire Quake design, from inlet to outlet, on the plate of
`
`Dale and/or Chien. Pet. 17 (“Because droplets produced by the emulsion
`
`generators are transmitted to the analysis units .
`
`.
`
`. one skilled in the art
`
`would have appreciated that high throughput is more readily accomplished
`
`using multiple droplet generators”), 36 (citing Ex. 1004 111] 71 (discussing
`
`the use of a “discrimination region” and associated detection regions in
`
`Quake), 77 (discussing the orientation of channels, detection regions, and
`
`wells or reservoirs in Quake’s “[s]orter embodiments”)); Ex. 1003 11 60 (Dr.
`
`Gandhi contemplating the use of “multiple droplet generators feeding
`
`multiple analysis units” based on Quake’s disclosures).
`
`Petitioner’s vaguely and inconsistently defined combination, of
`
`elements is not sufficient to allow for a reasoned analysis of the proposed
`
`combination or to allow proper consideration of whether one of ordinary
`
`skill in the art would have had a reasonable expectation of success in
`
`15
`
`

`

`IPR2018-00301
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`Patent 9,216,392 B2
`
`combining the teachings of the prior art references to arrive at the claimed
`
`invention. Pet. 27 (addressing only whether one of ordinary skill in the art
`
`would have had a reasonable expectation of success in including an array of
`
`emulsion production units on a single chip). This counsels against
`
`institution of review.
`
`b. Parallelizing Quake in view of both Quake and Dale
`
`Petitioner contends that, because it was well known in the art that
`
`parallelizing microfluidic circuits increases throughput, one of ordinary skill
`
`in the art would have found it obvious to provide a parallel array of Quake’s
`
`droplet generators on a single microfluidic chip. Pet. 18 (citing Ex. 1005
`
`1144; Ex. 1008 11 20; Ex. 1028, 12; Ex. 1012, 1—2; Ex. 1013 1111 92—93, 239;
`
`Ex. 1014 1] 75, Fig. 2). Petitioner further contends that, because Quake
`
`specifically suggests that providing multiple units on a single chip enables
`
`multiplexed processing of different samples, or the same sample by different
`
`processes, one of ordinary skill in the art would have been motivated “to use
`
`the teChnique taught in Dale (parallelization) to improve a similar device
`
`(Quake’s microfluidic device) in the same way (permit multiplex
`
`processing)” Id. at 18—19 (citing KSR, 550 US. at 415—421; Ex. 1003
`
`1111 60—65).
`
`Quake discloses implementing a linear array of channels and a
`
`“plurality of analysis units" on a single chip to provide a “multiplex system.”
`
`Ex. 1004 11 79 (disclosing that “linear arrays of channels on a single chip,
`
`i.e., a multiplex system, can simultaneously detect and sort a sample by
`
`using an array of photo multiplier tubes (PMT) for parallel analysis of
`
`different channels”). Quake also teaches or suggests providing multiple
`
`droplet generators on the chip. Id. 11 314 (disclosing that embodiments of the
`
`16
`
`

`

`IPR2018-00301
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`Patent 9,216,392 B2
`
`invention may “contain a plurality of droplet extrusion regions”); Ex. 1003
`
`1] 60 (testifying that “Quake discloses parallelizing the emulsion generating
`
`units”). Given that Quake already provides for a multiplexed system having
`
`parallelized emulsion generating units, we are not persuaded that one of
`
`ordinary skill in the art would have modified Quake in view of Dale in order
`
`to obtain these same features.
`
`Moreover, to the extent Petitioner contends an ordinary artisan would
`
`have sought to incorporate only the droplet generators of Quake on a single
`
`chip, without the analysis units and/or sorting channels, it is not evident why
`
`such a modification would have improved Quake’s device, which is
`
`designed for analyzing and/or sorting biological materials. Ex. 1004 1] 4,
`
`Abstract (“A microfluidic device for analyzing and/or sorting biological
`
`materials .
`
`.
`
`. and methods for its use are provided”); Pet. 19 (asserting that
`
`one of ordinary skill in the art would have sought to use Dale’s
`
`parallelization technique “to improve .
`
`.
`
`. Quake’s microfluidic device”).
`
`In view of the foregoing, Petitioner has not demonstrated sufficiently
`
`that one of ordinary skill in the art would have sought to modify Quake in
`
`View of Dale.
`
`(2. Use ofChien ’s Plate and Pressure Control System
`
`As noted above, Quake teaches driving fluids through its system using
`
`syringes pressurized with air. Ex. 1004 1] 288. Petitioner provides three
`
`reasons why it contends one of ordinary skill in the art would have sought to
`
`abandon Quake’s fluid drive system and adopt Chien’s multi-reservoir plate
`
`and pressure control system. Pet. 25—26.
`
`First, Petitioner contends one of ordinary skill in the art would have
`
`abandoned Quake’s pressurized air and syringe system in favor of “Chien’s
`
`17
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`multi-reservoir plate and pressure control system,” in view of Chien’s
`
`disclosure that “‘the use of external pumps to force liquids directly through
`9”
`
`microfluidic channels’ produces ‘irreproducible and erratic results
`
`and in
`
`view of Chien’s disclosure that the use of a compressible gas at the fluid-air
`
`interface on the top of the wells “is a more practical design.” Pet. 25
`
`(quoting Ex. 1035, 106).
`
`Consistent with Petitioner’s assertions, Chien indicates that accurate
`
`control of flow rate in microfluidic systems is extremely difficult and that a
`
`lack of proper control of small pressure differences will yield irreproducible
`
`and erratic results. Ex. 1035, 106. Chien does not disclose, however, that
`
`all external pumps yield irreproducible and erratic results in microfluidic
`
`systems, and neither Petitioner nor Dr. Gandhi asserts that Quake’s system
`
`suffers from a lack of pressure control or from irreproducible and erratic
`
`results. Indeed, any suggestion that Quake’s system lacks sufficient pressure
`
`control would appear to be expressly contradicted by Quake itself, which
`
`explains that the frequency of droplet production is “readily adjusted by
`
`simply adjusting the pressures of the individual fluid lines.” Ex. 1004
`
`1111 290, 296 (“As demonstrated here, the 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”); see also id 1] 79 (“Microfluidic pumps and valves are a
`
`preferred way of controlling fluid and sample flow.”). Thus, Petitioner has
`
`not demonstrated sufficiently that Chien’s disclosures would have motivated
`
`one of ordinary skill in the art to use Chien’s plate and pressure control
`
`system to drive fluid droplet generation in the emulsion generators of Quake.
`
`18
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`Second, Petitioner argues that modifying Quake to use Chien’s fluid
`
`drive system would allow an ordinary artisan to omit Quake’s external fluid
`
`reservoirs and pumps, which Dr. Gandhi testifies are expensive and need
`
`periodic cleaning. Pet. 26; Ex. 1003 ‘H 75 (“Eliminating tubing and pumps
`reduces cost and greatly reduces the risk of contamination”). We are not
`
`persuaded by this argument because, as noted by Patent Owner, Quake
`
`discloses that “the sorting devices of the invention are inexpensive and
`
`disposable, which obviates the need for cleaning and sterilization and
`
`prevents cross—contamination.” Ex. 1004 1] 14; Prelim. Resp. 30.
`
`Third, Petitioner argues that a skilled artisan would have been
`
`“strongly inclined to improve the Quake device” by implementing Chien’s
`
`fluid drive system, because “the syringe pumps, tubing, and wells of the
`
`Chien device were configured in a similar manner to Quake’s.” Pet. 26. As
`
`Patent Owner notes, however, a general similarity in structure or design
`
`between two devices is not a reason, in itself, to combine them. Prelim.
`
`Resp. 30—31. Thus, we are not persuaded that an alleged similarity in
`
`configuration is sufficient to demonstrate that one of ordinary skill in the art
`
`would have been motivated to combine Quake and Chien.
`
`In view of the foregoing, Petitioner has not explained sufficiently why
`
`one of ordinary skill in the art would have sought to implement multiple
`
`versions of Quake’s droplet generators on the plate of Dale and/or Chien, or
`
`why an ordinary artisan would have then sought to use Chien’s pressure
`
`control system to drive fluids through Quake’s droplet generators.
`
`Accordingly, Petitioner has not demonstrated a reasonable likelihood that
`
`independent claim 1 would have been obvious over the combined
`
`disclosures of Quake, Dale, Chien I, and Chien II.
`
`19
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`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`Because claims 2—6, 8, 10, 11, and 21 depend from claim 1, and
`
`because Petitioner’s arguments and evidence with respect to these claims do
`
`not remedy the defects identified above, Petitioner also has not demonstrated
`
`a reasonable likelihood that these claims would have been obvious over the
`
`combined disclosures of Quake, Dale, Chicn I, and Chien II.
`
`C. Remaining Grounds Based on Quake, Dale, Chien I, and Chien II
`
`Petitioner’s remaining challenges to dependent claims 7, 9, and 12—20
`
`require modification of the Combined System formed from Quake, Dale,
`
`Chien I, and Chien 11. Pet. 52, 54, 57, 69. Petitioner’s arguments with
`
`respect to these remaining challenges do not resolve the deficiencies noted
`
`above with respect to the combined teachings of Quake, Dale, Chien I, and
`
`Chien TI. Accordingly, Petitioner has not demonstrated a reasonable
`
`likelihood that dependent claims 7, 9, and 12—20 would have been obvious
`
`over the teachings of Quake, Dale, Chien I, Chien II in combination with
`
`Hsieh, Modlin, Soane, or Beer.
`
`111,
`
`CONCLUSION
`
`For the reasons discussed above, Petitioner has not demonstrated a
`
`reasonable likelihood that it would prevail with respect to at least one claim
`
`challenged in the Petition. Accordingly, we do not institute inter partes
`
`revicw.
`
`IV. ORDER
`
`It is hereby,
`
`ORDERED that no inter partes review is instituted.
`
`

`

`IPR2018-00301
`
`Patent 9,216,392 B2
`
`PETITIONER:
`
`Greg Gardella
`Natalie J. Grace
`
`GARDELLA GRACE P.A.
`
`ggardella@gardellagrace.com
`ngrace@gardellagrace.com
`
`Sarah Brashears
`
`CONVERGENT LAW GROUP LLP
`
`Ddevore@convergentlaw.com
`
`David J. Ball
`
`.
`
`PAUL, WEISS, RIFKIND, WHARTON & GARRISON LLP
`dball@paulweiss.com
`
`PATENT OWNER:
`
`James M. Glass
`
`Kevin Johnson
`
`Joseph Milowic III
`David Bilsker
`
`Nancy Zhang
`QUINN EMANUEL URQUHART & SULLIVAN
`jimglass@quinnemanuel.com
`kevinjohnson@quinnemanuel.com
`josephmilowic@quinnemanuel.com
`davidbilsker@quinnemanuel.com
`nancyzhang@quinnemanuel.com
`
`21
`
`

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