Trials@uspto. gov
`Tel: 571-272-7822
`
`P aper 1 3
`Entered: June 28, 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 IPR2018-00489
`
`Patent 9,500,664 B2
`
`Before KRISTINA M. KALAN, JON B. TORNQUIST, and
`JEFFREY W. ABRAHAM, Administrative PatentJudges.
`
`KALAN, Administrative Patent Judge.
`
`DECISION
`
`Denying Institution of Inter Partes Review
`35 US. C. §314(a)
`
`
`Tel: 571-272-7822
`
`P aper 1 3
`Entered: June 28, 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 IPR2018-00489
`
`Patent 9,500,664 B2
`
`Before KRISTINA M. KALAN, JON B. TORNQUIST, and
`JEFFREY W. ABRAHAM, Administrative PatentJudges.
`
`KALAN, Administrative Patent Judge.
`
`DECISION
`
`Denying Institution of Inter Partes Review
`35 US. C. §314(a)
`
`
`
`IPR2018-00489
`
`Patent 9,500,664 B7.
`
`1.
`
`INTRODUCTION
`
`10X Genomics, Inc. (“Petitioner”) filed a Petition (Paper 2, “Pet.”)
`
`requesting interpartes review of claims 1—1 6 of US. Patent No. 9,500,664
`
`B2 (Ex. 1001, “the ’664 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 interpartes
`
`review. 3 5 U. S.C. § 314. The standard for instituting an interpartes review
`
`is set forth in 35 U.S.C. § 314(a), which provides that an interpartes 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
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`institute an interpartes review.
`
`A. Related Proceedings
`
`The parties identify Bi0-Rad Laboratories, Inc. v. 1 0X Genomics, Inc,
`
`Case No. 3 :1 7-CV—4339 (N .D. Cal.) and Re: Certain Microfluidic Devices,
`
`Investigation Number 337-TA—1068 (ITC) as related matters. Pet. 3;
`
`Paper 4, 1. The parties also note that the ’664 patent is at issue in IPR2018-
`
`00490. Pet. 3; Paper 4, 1.
`
`B. The ’664 Patent
`
`The ’664 patent, titled “Droplet Generation for Droplet-Based
`
`Assays,” is a continuation of Application No. PCT/U$201 1/030101, and
`
`
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`IPR2018-00489
`
`Patent 9,500,664 B2
`
`claims priority to US. Provisional Application No. 61/341,218. Ex. 1001,
`
`at [54], [60], [63]. The ’664 patent is directed to a “system, including
`
`method and apparatus, for generating droplets suitable for droplet-based
`
`assays.” Id. at [57]. According to the ’664 patent: “This application
`
`incorporates by reference in their entireties for all purposes the following
`
`materials: US. Pat. NO. 7,041,481, issued May 9, 2006; US. Patent
`
`Application Publication No. 2010/0173394 A1, published Jul. 8, 2010; and
`
`Joseph R. Lakowicz, PRINCIPLES OF FLUORESCENCE SPECTROSCOPY (2"d
`
`Ed. 1999).” Id. at 1:17—22.
`
`Figures 8—10, reproduced below, depict an embodiment of a plate-
`
`based droplet generator of the ’664 patent:
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`
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`IPR2018-00489
`
`Patent 9,500,664 B2
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`Figure 8 is an isometric View of a top surface of a planar-mode droplet
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`generation system; Figure 9 is an isometric View of the bottom surface of the
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`same; Figure 10 is a magnified View of the bottom surface of the same. Id.
`
`at 2265—3 :4.
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`The ’664 patent has fifty-two figures depicting variations and features
`
`of the exemplary droplet generators “in accordance with aspects of the
`
`present disclosure.” Id. at Figs. 1—52, 2:46—4:48. Petitioner, however, does
`
`not rely on any of Figures 1—52 of the ’664 patent in its Grounds 1—4
`
`arguments. Pet. 21. Rather, Petitioner explains:
`
`Because the subject matter claimed the ‘664 is so similar to that
`described and claimed in [U.S. Patent No. 9,216,392] and [US
`Patent No. 9,126,160] and the grounds presented herein are so
`similar to those presented in the aforementioned IPRs [IPR2018-
`00302 and IPR2018-00434], for convenience and consistency
`the subject matter of the ‘664 patent is introduced with reference
`to certain figures of the ‘392 and ‘160 patents which are
`incorporated by reference into the ‘664 patent by virtue of their
`relationship to US. Patent Application Serial No. 12/586,626,
`which is incorporated by reference into the ‘664 patent.
`
`Id. at 18—19. Petitioner contends that Figures 4, 22, 23 and 24 of the ‘392
`
`and ’160 patents are illustrative.
`
`Id. at 16. Figure 24, reproduced below, is a
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`schematic view of a “four-port” droplet generator of the ’392 patent
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`(Ex. 1053) and the ’160 patent (Ex. 1050, 35:41—42):
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`
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`
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`IPR2018-00489
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`Patent 9,500,664 B2
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`In the droplet generator depicted in Figure 24, oil wells 1224 are loaded with
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`a carrier fluid (e.g., oil) and sample well 1226 is loaded with a sample (e. g.,
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`an assay mixture, such as a PCR mixture including a sample and a reagent).
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`Ex. 1050, 35:42—47. The wells are “connected fluidly by channels 1230
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`formed near the bottom” of the well. Id. at 35:3 5—3 7. The individual
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`channels connect at intersection 1232, where droplets are formed by “any
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`suitable mechanism, such as flow-focusing.” Id. at 35:37—40. The ’392 and
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`’160 patents explain 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
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`1228.” Id. at35z47—51.
`
`Figures 22 and 23 of the ’392 and ’ 160 patents are reproduced below:
`
`
`
`Figures 22 and 23 show exemplary device 1220 equipped with an array of
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`droplet generators 1222. Id. at 35:27—30. As shown in Figure 23, each
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`droplet generator 1222 may include wells or reservoirs 1224, 1226, and
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`IPR2018-00489
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`Patent 9,500,664 82
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`1228, which can be accessed from above plate 1220. Id. at 35:32—35. The
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`wells are fluidly connected by channels 1230. Id. at35:3 5—40.
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`C. Illustrative Claim
`
`Petitioner challenges claims 1—16 of the ’664 patent. Claims 1, 8, and
`
`14 are the independent claims of the ’664 patent. Claim 1 is illustrative and
`
`is reproduced. below:
`
`1. A system for forming a plurality of sample-containing
`droplets suspended in a background fluid, comprising:
`a substrate having a bottom surface and a top surface;
`a sample well, a background fluid well, and a droplet well each
`having an upper region protruding from the top surface of the
`substrate;
`a network of channels formed in the bottom surface of the
`substrate and fluidically interconnecting the sample well, the
`background fluid well, and the droplet well; and
`a droplet generation region defined by the network of channels
`and configured to generate sample-containing droplets
`suspended in the background fluid;
`wherein the droplet generation region is defined by the
`intersection of a first channel, a second channel, and a third
`
`channeh
`wherein the first channel is configured to transport sample-
`containing fluid from the sample well to the droplet generation
`region, the second channel is configured to transport
`background fluid from the background fluid well to the droplet
`generation region, and the third channelis configured to
`transport sample-containing droplets from the droplet
`generation region to the droplet well; and
`wherein the substrate and the upper region of each well are
`injection molded as a single piece.
`
`Ex. 1001, 43:55-44:14.
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`IPR2018-00489
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`Patent 9,500,664 B2
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`D. The Asserted Grounds of Unpatentability
`
`Petitioner contends claims 1—1 6 of the ’664 patent are unpatentable
`
`based on the following grounds (Pet. 24, 67, 70, 72):1
`
`
`
`
`
`
`
`
`Kumacheva,2 Modlin,3 and Mair4
`
`Kumacheva, Modlin, Mair, and Wang5
`
`Claims Challen-ed
`
`(1
`
`
`
`II. ANALYSIS
`
`
`
`
`
`
`
`
`A. Claim Construction
`
`In an interpartes review, claim terms in an unexpired patent are
`
`construed according to their broadest reasonable interpretation in light of the
`
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
`
`Cuozzo Speed Techs, LLCv. 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 ’664 patent require express construction
`
`for purposes ofthis Decision. See Nidec Motor Corp. v. Zhongshan Broad
`
`Ocean Motor Co. , 868 F.3d 1013, 1017 (Fed. Cir. 2017) (citing Vivid Techs,
`
`/
`
`‘ Petitioner also relies on a declaration from Dr. Khushroo Gandhi
`
`(Ex. 1003).
`2 US 2010/0184928 A1, published July 22, 2010 (Ex. 1004).
`3 US 2005/0266582 A1, published Dec. 1, 2005 (Ex. 1005).
`4 Mair, et al., Injection molded microfluidic chipsfeaturing i ntegrated
`interconnects, Lab on a Chip, 6:1346—1354 (2006) (Ex. 1047).
`5 US 2008/0257438 A1, published Oct. 23, 2008 (Ex. 1052).
`6 US 2002/0003001 A1, published Jan. 10, 2002 (Ex 1053).
`7 US 2008/0166720 A1, published July 10, 2008 (Ex. 1018).
`
`7
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`IPR2018-00489
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`Patent 9,500,664 B2
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`Inc. 12. 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, 5—8, and 12—1 6 over Kumacheva, Modlz'n, and Mair
`
`Petitioner contends the subject matter of claims 1, 5—8, and 12—16
`
`would have been obvious over the combined disclosures of Kumacheva,
`
`Modlin, and Mair. Pet. 24—67.
`
`I. Kumacheva (Ex. 1004)
`
`Kumacheva discloses “a multiple droplet generator integrating two or
`
`more parallel flow-focusing devices (FFDs).” Ex. 1004, Abstract. Figures 1
`
`and 2 of Kumacheva depict portions of the disclosed multiple droplet
`
`generator, and are reproduced below:
`
`6
`
`32
`34, /3
`APO—\F
`:Jl l
`: 38
`
`62
`
`32
`
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`
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`
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`
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`32 ”#36
`
`38
`
`FIG. 1
`
`FIG. 2
`
`Figure l is a schematic of droplet formation in an individual planar
`
`microfluidic flow-focusing droplet generator, and Figure 2 is a top view of
`
`an individual droplet generator depicting the direction of fluid flow. Id.
`
`1111 40—41.
`
`In the FFDs of Kumacheva, immiscible liquids A (droplet phase) and
`
`B (continuous phase) are combined to form an emulsion.
`
`Id. W 31, 61—63.
`
`Liquid A enters through opening 42 (Figure 2) and travels downstream
`
`through central microchannel30. Id. W 61—62. Liquid B enters through
`
`side microchannels 26 and travels downstream via microchannels 32. Id.
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`
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`IPR2018-00489
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`Patent 9,500,664 B2
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`As shown in more detail in Figure 1, liquids A and B are forced through
`
`narrow orifice 34 where “a thread of liquid A‘breaks up and releases droplets
`
`62” within outlet microchannel 38. Id. 11 61.
`
`Figure 3 of Kumacheva is reproduced below:
`
`
`
`Figure 3 shows a 3D illustration of four parallel flow-focusing devices 20.
`
`Id. 1] 63. As shown in Figure 3, the device of Kumacheva uses a single
`
`inlet 22 for the continuous phase, a single inlet 52 for the droplet phase, and
`
`a single outlet 64 to remove the droplets from the system. Id. 1111 2, 13
`
`(noting that the use of “two inlets for the droplet and continuous phases” can
`
`avoid “the use of multiple pumps supplying liquids to each microreactor”),
`
`20 (noting that “two or more parallel flow-focusing devices” are provided
`
`“with a single overall inlet branching into multiple inlets associated with
`
`each of the flow-focusing devices .
`
`.
`
`. and a single outlet”). After the
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`continuous phase is supplied through inlet 22, it is subsequently split into
`
`channels 26 and then channels 32 (shown in Figures 1 and 2). Id. 1] 66.
`
`After the droplet phase is injected into inlet 52, it is delivered to openings 42
`
`and subsequently travels through microchannels 30. Id. Droplets generated
`
`by flow-focusing devices 20 then travel through downstream channels 38 to
`
`outlet 64. Id.
`
`
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`IPR2018-00489 ’
`Patent 9,500,664 B2
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`2. Modlin (Ex. 1005)
`
`Modlin discloses a “microfluidic system for performing chemical
`
`reactions or biochemical, biological, or chemical assays utilizing a
`
`microfabricated device or ‘chip. ”’ Ex. 1005, Abstract. Figures 49 and 50 of
`
`Modlin are reproduced below:
`
`800
`
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`
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`
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`
`Fig. 49
`
`__A_s_ shown in Figure_49,_unit cell array 804_contains standard unitcells .820, _ _. - —
`
`which are replicated 96 times in “an industry standard 384 well format.” Id.
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`1] 209. As shown in Figure 50, each exemplary “4 port” standard unit
`
`cell 820 has four access ports that are each connected to at least one channel.
`
`Id. W 209—210.
`
`Figures 34 and 35 of Modlin are reproduced below:
`wen-.1.
`w“
`
`y‘gfik
`
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`
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`Fig. 35
`
`Figure 34 is a cross sectional perspective view of a microfluidic well plate,
`
`and Figure 35 is a partial cut away perspective view of the microfluidic well
`
`plate of Figure 34. Id. 1111 177—178. As shown in Figure 35, sample
`
`10
`
`
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`IPR2018-00489
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`Patent 9,500,664 B2
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`wells 614 are preferably positioned over access ports 622. Id. 1] 178.
`
`Channel 106f is formed between the surface of fabricated substrate 1 18f and
`
`the surface of membrane 1 10f and provides a fluid connection between
`
`access ports 622. Id. Modlin explains that the well to well spacing, or well
`
`pitch, of the standard unit cells “is designed to match industry standard
`
`microplate well pitches including but not limited to 96, 384, and 1536 well
`
`formats,” which ensures that the microfluidic well plates are “compatible
`
`with standardized fluid handling equipment.” Id. 1] 211.
`
`Figure 44 of Modlin, reproduced below, depicts pressure
`
`manifold 754 connected to microfluidic well plate 610:
`750
`752” 5
`
`759
`
`757
`
`752“ 758
`
`
`
`”mmflfl‘ew
`(Putkagud Chip)
`
`Fig. 44
`
`Manifold 775 may be mechanically aligned and sealably mounted to well
`
`plate 610 to distribute “pneumatic, hydraulic, electronic, mechanical, or
`
`optical signals” to their intended destinations on well plate 610. Id. 1111201—
`
`202.
`
`3. Mair (Ex. 1047)
`
`Mair is directed to an injection molding process for the fabrication of
`
`disposable plastic microfluidic chips. Ex. 1047, 1346. Mair teaches that
`
`well known manufacturing techniques, such as injection molding techniques,
`
`may be used for preparation of microfluidic systems from plastics. Id.
`
`Figure 5 of Mair is reproduced below:
`
`11
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`IPR2018-00489
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`Patent 9,500,664 B2
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`
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`Figure 5 of Mair shows a “[c]oncept of microfluidic chip featuring
`
`integrated ports (A) and a 4-port microfluidic chip with commercial male
`
`fittings threaded integrated ports of an injection molded chip (B).” Id.
`
`at 1351, Fig.5.
`
`4. Summary ofthe Pdrties ’Arguments
`
`Petitioner contends a skilled artisan would have found it obvious to
`
`configure Kumacheva’s FFD 36 in Modlin’s 3-1 combiner unit cell 822, as
`
`shown below (Pet. 30—3 1):
`
`
`
`In Petitioner’s proposed configuration, access ports 1 and 4 of unit cell 822
`
`contain the continuous phase and are connected to channels 32 of
`
`Kumacheva’s FFD. Id. Access port 3 of unit cell 822 contains the aqueous
`
`(dispersion) phase and is connected to channel 30 of Kumacheva’s FFD. Id.
`
`According to Petitioner, droplets are generated “at the cross-shaped
`
`junction” of Kumacheva and “routed through output channel 3 8 to output
`
`port 2.” Id. ; Ex. 1003 fl 57. Petitioner states that the “graphic below shows
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`12
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`IPR2018-00489
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`Patent 9,500,664 82
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`how the claimed subject matter corresponds to the Combined System of
`
`Kumacheva, Modlin and Mair” (Pet. 25):
`
`‘664 Patent
`
`System
`
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`
`XXXXXXXX
`
`XXXXXXXX
`
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`
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`
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`
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`
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`
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`
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`
`an‘fluhc
`
`Combined
`
`Petitioner contends the Combined System of Kumacheva, Modlin, and
`
`Mair teaches or suggests every limitation of independent claim 1. In
`
`particular, Petitioner contends the proposed device has a substrate having a
`
`bottom surface and a top surface (id. at 39—40), a sample well, a background
`
`13
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`IPR2018-00489
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`Patent 9,500,664 B2
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`fluid well, and a droplet well each having an upper region protruding from
`
`the top surface of the substrate (id. at 41—44), a network of channels formed
`
`in the bottom surface of the substrate and fluidically interconnecting the
`
`sample well, the background fluid well, and the droplet well (id. at 44—45),
`
`and a droplet generation region defined by the network of channels and
`
`configured to generate sample-containing droplets suspended in the
`
`background fluid, wherein the droplet generation region is defined by the
`
`intersection of a first channel, a second channel, and a third channel (id.
`
`at 45—47). Petitioner further contends that the first channel is configured to
`
`transport sample-containing fluid from the sample well to the droplet
`
`generation region, the second channel is configured to transport background
`
`fluid from the background fluid well to the droplet generation region, and
`
`the third channel is configured to transport sample-containing droplets from
`
`the droplet generation region to the droplet well (id. at 47—48), and that Mair
`
`teaches that the substrate and the upper region ofeach well are injection
`
`molded as a single piece (id. at 49—52).
`
`Petitioner contends one of ordinary skill in the art would have sought
`
`to make the proposed Combined System in order to increase the number of
`
`different droplet and continuous phases that may be used simultaneously, to
`
`permit analysis of multiple different samples from multiple different patients
`
`at the same time, to increase Kumacheva’s compatibility with standard fluid
`
`handling equipment, and to increase the degree of parallelization of
`
`Kumacheva’s device. Id. at 32—35. Petitioner further argues that one of
`
`ordinary skill in the art would have been motivated to make the
`
`substrate 118 and wells 614 by injection molding as a single piece, as
`
`suggested by Mair, because it eliminates the junction between the wells and
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`14
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`IPR2018-00489
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`Patent 9,500,664 B2
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`the substrate, it eliminates the need to align multiple parts prior to bonding,
`
`any number ofwells may be fabricated in the same period of time, and
`
`injection molding eliminates the use of glue. Id. at 50—51.
`
`Patent Owner contends Petitioner has failed to provide a reasoned
`
`explanation as to why one of ordinary skill in the art would have sought to
`
`combine Kumacheva, Modlin, and Mair in the manner proposed in the
`
`Petition. Prelim. Resp. 21—25. According to Patent Owner, “the centerpiece
`
`of the Petition .
`
`.
`
`. is actually nothing more than a collage of figures put
`
`together by Petitioner to follow the blueprint set forth in the ’664 patent,”
`
`which Patent Owner contends is “the epitome of impermissible hindsight.”
`
`Id. at 27.
`
`5. Analysis
`
`Although the elements of Petitioner’s Combined System appear
`
`similar to the elements of the droplet generator depicted in the priority
`
`documents referenced in ’664 patent, for the reasons set forth below, we
`
`agree with Patent Owner that neither Petitioner nor Dr. Gandhi explains
`
`persuasively why one of ordinary skill in the art, absent resort to hindsight
`
`and/or use of the ’664 patent as a roadmap, would have sought to make such
`
`a combination. See KSR Int ’1 Co. v. Teleflex Inc. , 550 US. 398, 418 (2007)
`
`(“[A] patent. .
`
`. is not proved obvious merely by demonstrating that each of
`
`its elements was, independently, known in the prior art”).
`
`First, P etitioner contends that Kumacheva discloses that adding
`
`manifolds may be useful where “mixing, concentration, dilution, or change
`
`in composition of droplet phase or continuous phases is needed,” and asserts
`
`that incorporating Modlin’s teaching of connecting each fluidic circuit to its
`
`own input and output well in a unit cell would “permit use of a wide variety
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`15
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`IPR2018-00489
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`Patent 9,500,664 B2
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`of different droplet phases and continuous phases on the same plate
`
`simultaneously, increasing efficiency of running large numbers of droplet
`
`generation operations.” Pet. 32—33; Ex. 100411 68; Ex. 1003 1] 59.
`
`Kumacheva’s device, however, already allows a user to change the
`
`composition of the droplet and/or continuous phases. Ex. 1004 1] 68. Thus,
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`it is not evident why an ordinary artisan would have combined Kumacheva
`
`and Modlin to achieve this result. It is also not evident why Kumacheva’s
`
`device, which is used to produce polymers, would benefit from the use of a
`
`wide variety of different droplet phases at the same time. Finally, to the
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`extent an ordinarily skilled artisan would have recognized a benefit in being
`
`able to use a wider variety of droplet and continuous phases than what
`
`Kumacheva’s device is capable of, Petitioner does not explain sufficiently
`
`why this ordinary artisan would have been prompted to abandon
`
`Kumacheva’s assertedly advantageous single inlet/single outlet design to
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`achieve this goal, much less have sought to do so in the device of Modlin,
`
`which was not designed to produce emulsions.8 Prelim. Resp. 22 (a person
`
`of ordinary skill in the art “would not read Kumacheva and then modify the
`
`FFDs of Kumacheva according to the designs of Modlin, which would result
`
`in more ‘inlets’ and ‘channels,’ not fewer”).
`
`Second, Petitioner also asserts that, because Kumacheva “expressly
`
`suggests” using the disclosed device “to perform biological and biochemical
`
`8 Petitioner and Dr. Gandhi assert that disposing Kumacheva’s droplet
`generators in a unit cell arrangement “would enable the droplet generators to
`be used to prepare and perform assays on a large number of different
`emulsions in parallel as disclosed by Modlin.” Ex. 1003 11 60; Pet. 22. We
`are directed to no disclosure in Modlin, however, of producing emulsions,
`much less a large number of different emulsions in parallel.
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`Patent 9,500,664 B2
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`analyses,” such as “DNA separation” and “parallel PCR assays,” one of
`
`ordinary skill in the art would have sought to implement Kumacheva’s
`
`droplet generator in Modljn to assay samples from multiple different patients
`
`on a single chip or, alternatively, to prepare different emulsions at the same
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`time. Pet. 33 (citing Ex. 1004 1] 14); Ex. 100311 60 (citing Ex. 1004 11 14).
`
`Contrary to Petitioner’s assertion, however, we are directed to no disclosure
`
`in Kumacheva ofusing the disclosed single inlet/single outlet droplet
`
`generators for “biological and biochemical assays,” “such as DNA
`
`separation” and “parallel PCR assays.” Ex. 1004 W 13 (discussing the
`
`challenges faced in scaling up the “microfluidic synthesis of polymer
`
`particles in multichannel microfluidic reactors”), 19 (“This present invention
`
`provides multiple continuous microfluidic reactors for parallel scaled up
`
`synthesis in polymer particles, and methods of use thereof”). The portion of
`
`Kumacheva relied upon by Petitioner is part of the “Background of the
`
`Invention” section, and distinguishes Kumacheva’s disclosed invention from
`
`certain prior art devices that “have been used” for, among other things,
`
`“DNA separation” and “parallel PCR assays.” Pet. 33 (citing Ex. 1004
`
`1] 14); see also Ex. 1004 1] 15 (“In these reports, emulsification in parallel
`
`combined microfluidic channels was not used”). Petitioner does not explain
`
`sufficiently why the generalized disclosure in the “Background of the
`
`Invention” section would have suggested using Kumacheva’s specific
`
`droplet generators for “biological and biochemical assays,” or why one of
`
`ordinary skill in the art would have been prompted to remove Kumacheva’s
`
`single inlet/single outlet design to do so. Prelim. Resp. 22 (asserting that
`
`Kumacheva “teaches the use of multiple substrates with as few ‘inlets’ and
`
`‘channels’ as possible”) (citing Ex. 1004 fl 15). The number ofmental steps
`
`17
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`and physical modifications necessary to achieve the proposed Combined
`
`System suggests it is proposed out of hindsight, and not in view of the
`
`knowledge and skill in the art as of the earliest priority date of the ’664
`
`patent. See Metalcraft ofMayvz'lle, Inc. v. The Tare C0. , 848 F.3d 1358,
`
`1367 (Fed. Cir. 2017) (“[W]e cannot allow hindsight bias to be the thread
`
`that stitches together prior art patches into something that is the claimed
`
`invention”). We note that this hindsight bias is evident in View of the fact
`
`that Petitioner did not even use figures from the ’664 patent in making its
`
`argument. The use of figures from an application incorporated by reference,
`
`though not per se improper, indicates that Petitioner needed to veer far off
`
`the course set by the ’664 patent to piece together a set of figures to match
`
`the “Combined System” used in its challenges. InTouch Techs., Inc. v. VGO
`
`Commc ’ns, Inc, 751 F.3d 1327, 1351 (Fed. Cir. 2014) (criticizing use ofthe
`
`challenged patent as a “roadmap” for putting what the expert referred to as
`
`“pieces of a ‘jigsaw puzzle’” together). This supports Patent Owner’s
`
`allegations of hindsight reconstruction. Prelim. Resp. 27.
`Third, Petitioner contends that one of ordinary skill in the art would
`
`have implemented Kumacheva’s droplet generator in Modlin in order to
`
`“substantially increase compatibility with industry standard laboratory
`
`equipment and reduce cost.” Pet. 33—34. According to Petitioner,
`
`configuring Kumacheva’s droplet generators according to Modlin’s
`
`microwell plate design would constitute the use of a known technique to
`
`improve similar devices in the same way. Id. (citing KSR, 550 US. at 41 5—
`
`421).
`
`The evidence of record supports Petitioner’s assertion that Modlin’s
`
`well plate design provides compatibility with industry standard equipment.
`
`18
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`Patent 9,500,664 B2
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`Ex. 1005 1111 105, 312; Pet. 33. As noted above, however, Petitioner’s
`
`Combined System involves abandoning Kumacheva’s single inlet/outlet
`
`design in favor of Modlin’s plate design. Petitioner does not adequately
`
`explain why one of ordinary skill in the art would have been prompted to
`
`abandon the single inlet/single outlet design of Kumacheva to increase '
`
`compatibility with certain industry standard equipment or to reduce costs.
`
`For example, Petitioner does not direct us to any evidence that Kumacheva’s
`
`design suffers from compatibility problems with industry equipment or cost
`
`issues. Nor does Petitioner explain why any such compatibility problems or
`
`cost issues could not be addressed by adjusting, as opposed to abandoning,
`
`Kumacheva’s single inlet/single outlet design that is the focus of the
`
`reference. Ex. 1004 W 2, 19—20 (utilizing “a single overall inlet branching
`
`into multiple inlets associated with each of the flow-focusing devices”),
`
`Figs. 2, 3; see Ex. 1005 {[1] 215—217, Figs. 54—55 (disclosing the use oftwo
`
`input wells and a routing network of channels in Modlin to deliver two
`
`common reagents to each unit cell). Petitioner’s proposed modifications
`
`once again appear to be proposed out of hindsight.
`
`Fourth, Petitioner contends that one of ordinary skill in the art would
`
`have sought to incorporate Kumacheva’ s droplet generator in the system of
`
`Modlin in order to “increase the degree of parallelization from four (as
`
`disclosed in Kumacheva) to 24, 96 or more.” Pet. 34—35 (asserting that
`
`paraIlelization of emulsion generators was well known in the art). This
`
`argument is not persuasive because, as Patent Owner notes, Kumacheva
`
`specifically discloses that its device may be used in “parallelization (scaling
`
`up) of the production of droplets” and is not limited to the use of only four
`
`droplet generators. Ex. 1004 W 20 (disclosing that the invention “can be
`
`19
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`IPR2018-00489
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`Patent 9,500,664 B2
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`used in parallelization,” and may have “two or more parallel flow-focusing
`
`devices”), 64 (noting that the device of Kumacheva is not limited to four
`
`droplet generators, and may have “a plurality” of flow-focusing devices 20),
`
`83 (describing the results of an integrated droplet generator comprising
`
`sixteen individual droplet generators); Prelim. ReSp. 24 (noting that
`
`Kumacheva specifically states that its design “can be used in parallelization
`
`(scaling up) of the production of droplets”) (quoting Ex 1004 1] 20).
`
`Moreover, even if one of ordinary skill in the art would have sought to
`
`increase parallelization beyond what Kumacheva’s device was capable of,
`
`Petitioner does not explain adequately why such an ordinarily skilled artisan
`
`would have been prompted to abandon the assertedly advantageous single
`
`inlet/single outlet design of Kumacheva to do so.
`
`Regarding Mair, Petitioner directs us to paragraphs 93—96 of the
`
`Gandhi Declaration to support its argument that a one of ordinary skill in the
`
`art would have a reason to incorporate Mair into the Combined System, and
`
`would have had a reasonable expectation of success in doing so. Pet. 49-5 2.
`
`Patent Owner responds that Kumacheva’ 3 devices “are constructed by
`
`lithographic means, not injection molding,” and that the “two techniques are
`
`very different” and “not necessarily compatible.” Prelim. Resp. 24. We
`
`note this argument; we also note that Modlin already teaches that injection
`
`molding may be used to make the substrate and wells, and Petitioner does
`
`not make clear why Modlin’s existing fabrication has any disadvantages that
`
`one of ordinary skill would seek to modify with Mair. Pet. 49 (citing
`
`Ex. 1005 11 160). Again, the reasoning for fabricating the Modlin substrates
`
`and wells by the methods ofMair appears to be proposed out of hindsight.
`
`See Metalcraft ofMayvz’ lle, 848 F.3d at 1367. Finally, as discussed above,
`
`20
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`IPR2018-00489
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`Patent 9,500,664 B2
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`we are unpersuaded by Petitioner’s reasoning supporting the existence of a
`
`Combined System formed of Kumacheva and Modlin. Petitioner’s
`
`reasoning supporting the proposed integration of Mair into the Combined
`
`System does not overcome this shortfall.
`
`In view of the foregoing, Petitioner has not explained sufficiently why
`
`one of ordinary skill in the art would have sought to combine the identified
`
`disclosures of Kumacheva, Modlin, and Mair to arrive at the subject matter
`
`of the ’664 patent. Accordingly, Petitioner has not demonstrated a
`
`reasonable likelihood that the subject matter of claims 1, 5—8, and 12—16
`
`would have been obvious over Kumacheva, Modlin, and Mair.
`
`C. Remaining Grounds Based on Kumacheva, Mod]in, and Mair
`
`Each of the remaining grounds asserted in the Petition relies, at least
`
`in part, on the combined teachings of Kumacheva, Modlin, and Mair.
`
`Pet. 67—75. Petitioner’s arguments and supporting evidence with respect to
`
`these additional grounds do not resolve the deficiencies noted above with
`
`respect to the reasons to combine Kumacheva, Modlin, and Mair in the
`
`manner proposed in the Petition. Accordingly, Petitioner has not
`
`demonstrated areasonable likelihood that the challenged claims would have
`
`been obvious over the recited prior art references.
`
`III.
`
`CONCLUSION
`
`For the forgoing reasons, Petitioner has not demonstrated a reasonable
`
`likelihood that at least one challenged claim of the ’664 patent would have
`
`been obvious over the prior art of record. Accordingly, we do not institute
`
`interpartes review.
`
`21
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`IPR2018-00489
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`Patent 9,500,664 B2
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`It is hereby,
`
`IV. ORDER
`
`ORDERED that, pursuant to 35 U. 8.0 § 314, the Petition is denied
`
`and no interpartes review is instituted.
`
`22
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`IPR2018-00489
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`Patent 9,500,664 B2
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`FOR PETITIONER:
`
`Greg Gardella
`ggardellaganrdeflagace.corn
`
`Dianna DeVore
`
`ddevorechonvergentlaw.com
`
`Sarah Brashears
`
`sbrashears@convergentlaw.com
`
`FOR PATENT OWNER:
`
`J irn Glass
`
`1' im glassgaZQuinnemanu el. com
`
`Kevin Johnson
`
`kevinj ohnson@guinnemanue1.com
`
`David Bilsker
`
`davidbilsker@guinnemanuel. com
`
`Joseph Milowic III
`josephmilowic@guinnemanuel.com
`
`Nancy Zhang
`nzhan ws
`
`.com
`
`23
`
`
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