Trials@uspto.gov
`Tel: 571-272-7822
`
`Paper 7
`Entered: December 10, 2018
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`10X GENOMICS, INC.,
`
`Petitioner,
`
`V.
`
`BIO-RAD LABORATORIES, INC.,
`
`Patent Owner.
`
`Case IPR2018-01206
`
`Patent 9,649,635 B2
`
`Before KRISTINA M. KALAN, JON B. TORNQUIST, and
`DEBRA L. DENNETT, Administrative Patent Judges.
`
`DENNETT, Administrative Patent Judge.
`
`DECISION
`
`Denying Institution of Inter Partes Review
`35 USC. § 314(a)
`
`

`

`IPR2018-01206
`
`Patent 9,649,635 B2
`
`I.
`
`INTRODUCTION
`
`10X Genomics, Inc. (“Petitioner”) filed a Petition (Paper 1, “Pet.”)
`
`requesting inter partes review of claims 1—27 of US. Patent
`
`No. 9,649,635 B2 (Ex. 1001, “the ’635 patent”). Bio-Rad Laboratories, Inc.
`
`(“Patent Owner”) filed a Preliminary Response to the Petition (Paper 6,
`
`“Prelim. Resp.”).
`
`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 deny the Petition, and do not
`
`institute an inter partes review.
`
`.A. 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
`
`4, 1. The parties also note that the ’635 patent is at issue in IPR2018—01207.
`
`Pet. 1; Paper 4, 1.
`
`B. The '635 Patent
`
`The ’635 patent, titled “System for Generating Droplets with Push-
`
`Back to Remove Oil,” is directed to a “[s]ystem, including methods,
`
`

`

`IPR2018-01206
`
`Patent 9,649,635 B2
`
`apparatus, and kits, for forming and concentrating emulsions” that “may
`
`comprise a device including a sample well configured to receive sample-
`
`containing fluid, a continuous-phase well configured to receive continuous-
`
`phase fluid, a droplet well, and a channel network interconnecting the
`
`wells.” Ex. 1001, at [54], [57]. The instrument may apply pressure to
`
`emulsion phases held by a microfluidic chip to drive formation and
`
`collection of emulsions in the chip. Id. at 4:63—65. Figure 6 of the ’635
`
`patent is reproduced below:
`
`
`
`Figure 6 of the ’635 patent is an exploded View of microfluidic chip 152. Id.
`
`at 3:64—67, 4:4. Figure 6 shows upper member 180 forming a bottom region
`
`or base 184 and a plurality of tubular projections forming lateral side walls
`
`188 of one of wells 168—170. Id. at 11:63—67. Lower member 182 may
`
`form a bottom wall of each of wells 168—172. Id. at 12:2—4.
`
`Figure 11 of the ’635 patent is reproduced below:
`
`

`

`IPR2018-01206
`
`Patent 9,649,635 B2
`
`Fig. 1.1
`2001
`
` 212
`
`Figure 11 of the ’635 patent is a “less schematic bottom View of the single
`
`emulsion formulation unit” depicted in Figure 9, which is a “somewhat
`
`schematic bottom View of a single emulsion formation unit of the chip of
`
`FIG. 6.” Id. at 4:9—10, 4:15—16. As shown in Figure 11, which depicts the
`
`bottom View of one of the units of chip 152, wells 168, 170, and 172 are
`
`connected by network of channels 210—216, which intersect at and form
`
`droplet generator 198. Id. at 12:55—13:23. At droplet generator 198,
`
`droplets of sample fluid are generated, creating an emulsion that may be
`
`received and collected at output well 172. Id. at 1225—15.
`
`Figure 20 of the’635 patent is reproduced below:
`
`Fig. 20-
`
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`
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`
`
`Figure 20 is a sectional view of the manifold, chip, and gasket of Figure 19.
`
`Id. at 4:44—46. Figure 20 shows manifold 72, chip 152, gasket 154, ports 76,
`
`row of gasket orifices 176, and wells 172. Id. at 21:55—57. Main channel
`
`430 may be fluidically connected to each well 172. Id. at 21:64—65.
`
`Pressure may be applied to wells 172 Via manifold 72. Id. at 22: 12—19.
`
`4
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`

`

`IPR2018-01206
`
`Patent 9,649,635 B2
`
`C. Illustrative Claims
`
`Petitioner challenges claims 1—27 of the ’635 patent. Independent
`
`claims 1, 16, and 23, reproduced below, are illustrative of the challenged
`
`claims:
`
`1. A system to form and generate an emulsion, comprising:
`
`a device including a sample well configured to receive sample-
`containing fluid, a continuous-phase well configured to receive
`continuous—phase fluid, and a droplet well, the device also
`including a channel network having a first channel, a second
`channel, and third channel that meet one another in a dr0plet-
`generation region; and
`
`an instrument configured to operatively receive the device and
`to create
`
`(a) a first pressure differential to drive sample-
`containing fluid from the sample well to the droplet-
`generation region Via the first channel, continuous-phase
`fluid from the continuous-phase well to the droplet
`generation region via the second channel, and sample-
`containing droplets from the droplet-generation region to
`the droplet well via the third channel, such that the
`droplet well collects an emulsion including sample-
`containing droplets disposed in continuous-phase fluid,
`and
`
`(b) a second pressure differential to decrease a volume
`fraction of continuous-phase fluid in the emulsion, after
`the emulsion has been collected in the droplet well, by
`selectively driving continuous-phase fluid, relative to
`sample-containing droplets, from the droplet well via the
`third channel.
`
`16. A system to form and concentrate emulsions, comprising:
`
`a device including a row of sample wells each configured to
`receive sample-containing fluid, a row of continuous-phase
`wells each configured to receive continuous-phase fluid, a row
`
`

`

`IPR2018-01206
`
`Patent 9,649,635 BZ
`
`of droplet wells, and a plurality of separate channel networks,
`each sample well being fluidically connected to one of the
`continuous-phase wells mid one of the droplet wells via one of
`the channel networks, each channel network having a first
`channel, a second channel, and a third channel that meet one
`another in a droplet—generation region;
`
`a gasket configured to operatively engage at least one of the
`rows of wells; and
`
`an instrument including a manifold, the instrument being
`configured to operatively engage the gasket with the manifold
`such that the manifold is sealed to each well or the al least one
`
`rows or wells, and to create via the manifold
`
`(a) a first pressure differential to drive sample-
`containing fluid from each sample well and continuous-
`phase fluid from each continuous-phase well, such that
`sample-containing droplets are formed in the droplet-
`generation region of each channel network and travel via
`the third channel of the channel network to one of the
`droplet wells for collection as an emulsion including
`sample-containing droplets disposed in continuous-
`phase fluid, and
`
`(b) a second pressure differential to decrease a volume
`fraction of continuous-phase fluid in each emulsion,
`after the emulsion has been collected in the one droplet
`well, by selectively driving continuous-phase fluid,
`relative to sample—containing droplets, from the one
`droplet well via the third channel.
`
`23. A method of forming and concentrating an emulsion, the
`method comprising:
`
`driving sample-containing fluid in a first channel and
`continuous-phase fluid in a second channel to a droplet-
`generation region in which the first and second channels meet
`one another, such that sample-containing droplets are formed;
`
`driving sample-containing droplets and continuous-phase fluid
`from the droplet—generation region to a well via a third
`
`6
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`

`

`IPR2018-01206
`
`Patent 9,649,635 B2 '
`
`channel, such that an emulsion including sample-containing
`droplets disposed in continuous-phase fluid is collected in the
`well: and
`
`decreasing a volume fraction of continuous-phase fluid in the
`emulsion by selectively driving continuous-phase fluid,
`relative to the droplets, from the well via the third channel.
`
`Ex. 1001, 33:29—55; 34:52—35:18; 36:6—21.
`
`D. The Asserted Grounds of Unpatentability
`
`/
`
`Petitioner contends claims 1—27 of the ’635 patent are unpatentable
`
`based on the following grounds (Pet. 17, 54, 71, 74, 76, 77):1
`
`References
`Claims Challened
`Ismagilovz, Chien13, Chien H4, and
`§ 103
`1—8 and 11—27
`
`Holtze5
`
`§ 103
`
`9 and 10
`
`Ismagilov, Chien I, Chien II, Holtze,
`
`and Ito6
`
`
`
`II. ANALYSIS
`
`A. Claim Construction
`
`In an inter partes review, claim terms in an unexpired patent are
`
`construed according to their broadest reasonable interpretation in light of the
`
`' Petitioner also relies on a declaration from Dr. Khushroo Gandhi
`
`(Ex. 1003).
`2 US 2005/0087122 A1, published April 28, 2005 (Ex. 1004).
`3 US 6,915,679 B2, issued July 12, 2005 (Ex. 1005).
`4 Ring-Ling Chien & J. Wallace Parce, Multiportflow-control system for
`lab-on-a-chip microfluidic devices, Fresenius J. Anal. Chem. 371:106—1 11
`(2001) (Ex. 1006).
`5 Holtze, et al., Biocompatible surfactants for water-in-fluorocarbon
`emulsions, Lab on a Chip, The Royal Society of Chemistry, 8(10):1632—
`1639 (2008) (Ex. 1008).
`6 US 2011/0046243 A1, published February 24, 2011 (Ex. 1007).
`
`7
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`IPR2018-01206
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`Patent 9,649,635 B2
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`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).7
`
`Upon review of the parties’ arguments and supporting evidence, we
`
`determine that no claim. terms of the ’635 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—8 and 11—27 over Ismagilov, Chien 1, Chien II, and
`Holtze
`
`Petitioner contends the subject matter of claims 1—8 and 11—27 would
`
`have been obvious over the combined disclosures of Ismagilov, Chien I,
`
`Chien II, and Holtze. Pet. 15—69.
`
`1. Ismagilov (Ex. 1004)
`
`Ismagilov, titled “Device and Method for Pressure-Driven Plug
`
`Transport and Reaction,” is directed to “microfabricated substrates and
`
`methods of conducting reactions within these substrates.” Ex. 1004, at [54],
`
`[57]. The methods of Ismagilov involve “conducting a reaction within a
`
`7 The revised claim construction standard for interpreting claims in inter
`partes review proceedings as set forth in the final rule published October 11,
`2018, does not apply to this proceeding, because the new “rule is effective
`on November 13, 2018 and applies to all IPR, PGR and CBM petitions filed
`on or after the effective date.” Changes to the Claim Construction Standard
`for Interpreting Claims in Trial Proceedings Before the Patent Trial and
`Appeal Board, 83 Fed. Reg. 51340 (Oct. 11, 2018) (to be codified at 37
`CPR. pt. 42).
`
`

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`IPR2018-01206
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`Patent 9,649,635 B2
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`substrate” that comprises “introducing a carrier-fluid into a first channel of
`
`the substrate; introducing at least two different plug-fluids into the first
`
`channel; and applying pressure to the first channel to induce a fluid flow in
`
`the substrate to form substantially identical plugs comprising a mixture of
`
`plug-fluids.” Id. 11 10. Ismagilov’s substrate “can be fabricated with a fluid
`
`reservoir or well at the inlet port, which is typically in fluid communication
`
`with an inlet channel.” Id. 11 143.
`
`lsmagilov’s “inlet port” refers to “an area
`
`of a substrate that receives plug-fluids” and which “may contain an inlet
`
`channel, a well or reservoir, an opening, and other features that facilitate the
`
`entry of chemicals into the substrate.” Id. 11 93. Regarding its “outlet port,”
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`Ismagilov provides that it is “an area of a substrate that collects or dispenses
`
`the plug-fluid, carrier-fluid, plugs or reaction product.” Id. 11 96.
`
`Figure 2A-2 of Ismagilov is reproduced below:
`
`
`
`d==0
`
`.
`
`a,
`
`Ha. 21:72 '
`
`. In Figure 2A-2, two aqueous reagents form laminar streams that are
`
`separated by a “divider” aqueous stream. Id. 11 150. “The three streams
`
`enter a channel with flowing oil, at which point plugs form and plug fluids
`
`mix.” Id.. Ismagilov teaches that, when introducing fluids, typically “a
`
`syringe pump is used, wherein the flow rate of the fluid into the inlet can be
`
`controlled.” Id. 11 127. Ismagilov also teaches introducing fluids into the
`
`substrate “through pneumatically driven syringe reservoirs.” Id. 11 171.
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`

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`IPR2018-01206
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`Patent 9,649,635 B2
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`2. Chien I (Ex. 1005)
`
`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. 1005, 2:56—61. Figure 1 of Chien I is
`
`reproduced below:
`
`
`
`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 devicc 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):
`
`
`
`

`

`IPR2018-01206
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`Patent 9,649,635 B2
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`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 microfluidic 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. Id. at 10:57—61.
`
`3. Chien 11 (Ex. 1006)
`
`Chien 11 describes the same embodiment as Chien I. Pet. 21. Chien II
`
`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 of 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.
`
`4. Ex. 1006, 106. Chien II indicates thatflow may be positive or
`negativeHoltze (Ex. 1008)
`
`Holtze, titled “Biocompatible surfactants for water-in-fluorocarbon
`
`emulsions,” describes development of non-ionic fluorosurfactants for use
`
`with microfluidic devices. Ex. 1008, 2.8 As one of several tests of the
`
`performance of the surfactant, drops with a self-assembled layer of
`
`8 Citations are to the page numbers added by Petitioner in the lower right
`corner of the reference.
`
`11
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`

`

`IPR2018-01206
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`Patent 9,649,635 82
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`surfactant molecules at the interface between the fluorocarbon oil and
`
`aqueous phases were stored in polydimethylsiloxane microchannels for three
`
`days. Id. at 3, 5. Holtze states that drops are typically compressed by
`
`draining the oil, in order to test as many drops as possible. Id. at 5.
`
`5. Analysis
`
`Petitioner contends one of ordinary skill in the art would have found it
`
`obvious to combine the teachings of Ismagilov, Chien I, Chien II,9 and
`
`Holtze to form a “Combined System” that includes every limitation of
`
`independent claim 1. Pet. 18—47. The Combined System, as depicted by
`
`Petitioner, is reproduced below:
`
`Paraltel Arrays of
`Droplet Generators with Wells
`
`reactors may be operated in parallel
`to provide substantial throughput."
`11116
`
`"Each of the outlet and inlet ports
`may also communicate with a well or
`
`reservoir." 11127
`
`2’.
`
`F13. 1
`
`Id. at 24.
`
`Petitioner contends that the Chien references “explain that the well
`
`structure disclosed in Ismagilov advantageously permits use of pressurized
`
`9 We refer to Chien I and Chien II collectively as “Chien.”
`
`12
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`IPR2018-01206
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`Patent 9,649,635 B2
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`air to drive the fluids from the wells and through the microfluidic circuit,
`
`which substantially improves precision of the microfluidic control.” Id.
`
`at 16. Petitioner argues that Holtze “teaches that it is advantageous to
`
`concentrate the droplets by removing the excess continuous phase.” Id.
`
`More particularly, Petitioner contends that Ismagilov discloses
`
`microfluidic droplet or emulsion generators provided on a microfluidic
`
`device (id. at 18—19), each of the channels of the droplet generator
`
`connected to input wells and an output well (id. at 19), and that an array of
`
`droplet generators may be disposed on a single substrate to improve
`
`throughput (id. at 20). Petitioner contends that Chien teaches that it is
`
`preferred to mount the chip to a pneumatic manifold that provides air
`
`pressure to drive fluids between the wells (id. at 21), and that a skilled
`artisan would have found it obvious to use Chien’s instrument to drive fluids
`
`through Ismagilov’s emulsion generators. Id. at 27—29.
`
`Petitioner contends that one of ordinary skill in the art would have
`
`sought to implement “Chien’s multi-reservoir device and pressure control
`
`system to drive the fluids through the emulsion productions units of
`
`Ismagilov,” because Chien’s control of pressure at the fluid-air interface at
`
`the top of the wells is a more practical design, because it would simplify the
`
`bench—top instrument and reduce the risk of contamination, and because
`
`Chien and Ismagilov use similar equipment. Id. at 28—29.
`
`Petitioner also asserts that it would have been obvious to use Chien’s
`
`reverse flow to drain the excess continuous phase from the droplet well so as
`
`to store the droplets in the tightly packed manner illustrated in Holtze. Id. at
`
`31. Petitioner contends incubating droplets in on-chips wells was known to
`
`be superior to incubation in delay lines and that this modification would
`
`13
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`IPR2018-01206
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`Patent 9,649,635 B2
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`allow one to incubate far more aqueous droplets in a given reservoir and
`
`would reduce the risk of spillage when the microfluidic chip is removed and
`
`transported.
`
`Id. at 32.
`
`Patent Owner argues Petitioner fails to provide a reasonable
`
`explanation as to why one of ordinary skill in the art would have sought to
`
`combine Ismagilov, Chien, and Holtze. Prelim. ReSp. 21—27. Patent Owner
`
`asserts Petitioner does not explain why Chien would have motivated one of
`
`ordinary skill in the art to modify Ismagilov to incorporate Chien’s fluid
`
`drive technique. Id. Patent Owner contends the proposed integration of
`
`Holtze does not overcome the shortfalls of the combination of Ismagilov and
`
`Chien. Id. at 23.
`
`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 Ismagilov, Chien, and Holtze to arrive at the subject matter of the
`
`challenged claims.
`
`As a preliminary matter, we find the proposed combination of
`
`Ismagilov, Chien, and Holtze is not clearly defined. Petitioner asserts that it
`
`would have been “obvious to use Chien’s instrument to drive the fluids
`
`through lsmagilov’s emulsion generators.” Pet. 23, 16 (relying on “the well
`
`structure disclosed in Ismagilov”); Ex. 1003 11 61 (“[O]ne of ordinary skill in
`
`the art would have considered it obvious to-use Chien’s system to drive
`
`fluids through Ismagilov’s emulsion generators”). From this statcment, and
`
`based on the Combined System, it appears that Petitioner proposes to place
`
`Chien’s instrument atop Ismagilov’s emulsion generators. This is the
`
`combination of elements Patent Owner addresses and criticizes in the
`
`.14
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`

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`IPR2018-01206
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`Patent 9,649,635 B2
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`Preliminary Response. Prelim. Resp. 21—27, 23 n.4 (criticizing Petitioner’s
`
`assertion that “[p]roviding Ismagilov’s emulsion production unit on a
`
`microfluidic chip and interfacing that chip with Chien’s pneumatic drive
`
`system would require no more than routine skill and would lead to
`
`predictable results.” (Citing Pet. 34)).
`
`Other portions of the Petition, however, appear to contemplate
`
`different combinations than the foregoing. Ex. 1003 1] 64 (Dr. Gandhi
`
`contemplating that “[Ismagilov’s] droplet generator is incorporated into the
`
`microfluidic device 12 of Chien”); 11 68 (“[O]ne of ordinary skill in the art
`
`would have found it routine to improve the Ismagilov [sic] microfluidic
`
`device with the compatible techniques taught by Chien”); Pet. 25 (“To the
`
`extent Ismagilov is not considered to sufficiently teach that the input and
`
`output ports both have wells, Chien teaches that feature”). Petitioner’s
`
`occasional reliance on Chien’s input wells, output wells, and microfluidic
`
`device in the alternative renders its proposed combination unclear in view of
`
`its representations that Chien’s pneumatic drive system is used with
`
`Ismagilov’s emulsion production unit.
`
`Petitioner’s alternatively 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
`
`combining the teachings of the prior art references to arrive at the claimed
`
`invention. Pet. 34 (addressing whether one of ordinary skill in the art would
`
`have had a reasonable expectation of success in “[p]roviding Ismagilov’s
`
`emulsion production unit on a microfluidic chip and interfacing that chip
`
`15
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`IPR2018-01206
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`Patent 9,649,635 B2
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`with Chien’s pneumatic drive system”). This counsels against institution of
`
`review.
`
`As noted above, Ismagilov teaches driving fluids through its system
`
`“through pneumatically driven syringe reservoirs.” Ex. 1004 11 171.
`
`Petitioner provides three reasons why it contends one of ordinary skill in the
`
`- art would have sought to adopt “Chien’s multi-reservoir device and pressure
`
`control system to drive the fluids through the emulsion productions units of
`
`Ismagilov.” Pet. 28—29.
`
`First, Petitioner contends one of ordinary skill in the art would have
`
`used “Chien’s multi-reservoir device and pressure control system,” in view
`
`of Chien’s disclosure that “‘the use of external pumps to force liquids
`
`directly through microfluidic channels’ produces relatively
`
`‘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.” Id. (quoting Ex. 1006, 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. 1006, 106. Chien does not disclose, however, that
`
`all pumping systems yield irreproducible and erratic results in microfluidic
`systems, and neither Petitioner nor Dr. Gandhi asserts that Ismagilov’s
`system suffers from a lack of pressure control or from irreproducible and
`
`erratic results. Indeed, any suggestion that Ismagilov’s system lacks
`
`sufficient pressure control would appear to be contradicted by Ismagilov
`
`itself, which explains that introduction of fluids “may be under pressure
`
`according to a given flow rate” that “may be constant or varied with respect
`
`16
`
`

`

`IPR2018-01206
`
`Patent 9,649,635 B2
`
`to another inlet” or “administered at a constant or a variable flow rate.”
`
`Ex. 1004 fl 16; see also id. 11 171 (plugs may be produced “by modifying the
`
`relative pressures”); 11 172 (“The force and direction of flow can be
`
`controlled by any desired method for controlling flow, for example, by a
`
`pressure differential, or by valve action”); 11 174 (“If desired, the pressure
`
`can be adjusted or equalized”). Thus, Petitioner has not demonstrated
`
`sufficiently that one of ordinary skill in the art would have been prompted to
`
`use Chien’s device and pressure control system to drive fluid droplet
`
`generation in the emulsion generators of Ismagilov.
`
`Second, Petitioner argues that modifying Ismagilov to use Chien’s gas
`
`drive technique “simplifies the bench-top instrument and reduces the risk of
`
`contamination” in that it “may omit fluid reservoirs or pumps which are both
`
`expensive and need periodic cleaning.” Pet. 29; Ex. 1003 11 67
`
`(“[E]liminating tubing and pumps reduces cost and greatly reduces the risk
`
`of contamination”). We are not persuaded by this argument because
`
`Petitioner directs us to no evidence that Ismagilov’s system has problems
`
`with complexity, undue expense, or contamination. See also Prelim.
`
`Resp. 22 (citing Ex. 1004 1] 113 (“In accordance with the devices and
`
`methods according to the invention, the surface chemistry to which solutions
`
`are exposed is preferably controlled through a careful selection of
`
`surfactants that are preferably designed to assemble at the interface between
`
`the plugs and the immiscible fluid that surrounds them.”). Additionally,
`
`Petitioner does not explain adequately how one of ordinary skill in the art
`
`would eliminate fluid reservoirs, tubing, and pumps to avoid the purported
`
`problems of expense, complexity, and contamination, particularly in view
`
`Petitioner’s proposed Combined System, which appears to retain and rely
`
`l7
`
`

`

`IPR2018-01206
`
`Patent 9,649,635 B2
`
`upon the tubing and pumps of Chien. See Pet. 24; Ex. 1005, Fig. l, 9:43—57.
`
`Petitioner’s reasoning on this point is insufficient to support institution of
`
`inter partes review.
`
`Third, Petitioner argues that a skilled artisan would have been
`
`“strongly inclined to improve the Ismagilov device” by implementing
`
`Chien’s techniques, because “the syringe pumps, tubing, and wells of the
`
`Chien device were configured in a similar manner to Ismagilov’s.” Pet. 29.
`
`As Patent Owner notes, however, a general similarity in structure or design
`
`between two devices is not a reason, in itself, to combine those devices.
`
`Prelim. Resp. 22—23. 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 Ismagilov and Chien.
`
`Petitioner turns to Holtze as teaching draining the oil (continuous
`
`phase) from the droplet well in order to tightly pack, and therefore test, as
`
`many drops as possible. Pet. 31. Petitioner contends that it would have been
`
`obvious to use Chien’s reverse flow to drain the excess continuous phase
`
`from the droplet well so as to store the droplets in the tightly packed manner
`illustrated in Holtze. 1d. These arguments, however, do not overcome or
`
`remedy the deficiencies noted above with respect to the combination of
`
`Ismagilov and Chien.
`
`In view of the foregoing, Petitioner has not explained sufficiently why
`
`one of. ordinary skill in the art would have sought to use Chien’s pressure
`
`control system to drive fluids through Ismagilov’s droplet generators.
`
`Accordingly, Petitioner has not demonstrated a reasonable likelihood that
`
`independent claim 1 would have been obvious over the combined
`
`disclosures of Ismagilov, Chien I, Chien II, and Holtze.
`
`l8
`
`

`

`IPR2018—01206
`
`Patent 9,649,635 B2
`
`Petitioner’s arguments for obviousness of independent claims 16 and
`
`23, as well as dependent claims 2—8, 11—15, 17—22, and 24—27, rely on the
`
`same evidence. and reasoning as for independent claim 1. Pet. 48—69. Thus,
`
`Petitioner does not demonstrate a reasonable likelihood that these claims
`
`would have been obvious over the combined disclosures of Ismagilov, Chien
`
`I, Chien II, and Holtze.
`
`C. Remaining Ground Based on Ismagilov, Chien I, Chien II, Holtze,
`and Ito
`
`The remaining ground asserted in the Petition a’gainst claims 9 and 10
`
`relies, at least in part, on the combined teachings of Ismagilov, Chien I,
`
`Chien II, and Holtze. Pet. 70—76. Petitioner’s arguments and supporting
`
`evidence with respect to this additional ground does not resolve the
`
`deficiencies noted above with respect to the reasons to combine Ismagilov,
`
`Chien I, Chien II, and Holtze in the manner proposed in the Petition.
`
`Accordingly, Petitioner has not demonstrated a reasonable likelihood that
`
`the challenged claims would have been obvious over the recited prior art
`
`references.
`
`III.
`
`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
`
`review.
`
`IV. ORDER
`
`It is hereby,
`
`ORDERED that no inter partes review is instituted.
`
`l9
`
`

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