UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`
`
`10X GENOMICS, INC.
`Petitioner
`
`v.
`
`RAINDANCE TECHNOLOGIES, INC.
`Patent Owner
`
`_____________________
`
`Case IPR2015-01558
`U.S. Patent No. 8,658,430
`_____________________
`
`PETITIONER’S DEMONSTRATIVES
`FOR ORAL ARGUMENT
`
`
`
`
`
`
`
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`
`
`10X GENOMICS, INC.
`Petitioner
`
`v.
`
`RAINDANCE TECHNOLOGIES, INC.
`Patent Owner
`
`_____________________
`
`Case IPR2015-01558
`U.S. Patent No. 8,658,430
`_____________________
`
`PETITIONER’S DEMONSTRATIVES
`FOR ORAL ARGUMENT
`
`
`
`
`
`
`
`
`Before MICHAEL P. TIERNEY, TINA E. HULSE, and ELIZABETH M.
`ROESEL, Administrative Patent Judges.
`
`September 27, 2016
`
`
`
` Claims 1-7 and 12-17 are anticipated by Link
`
`[Pet., Paper 2, at 17-35; Huck Dec #1, GEN1002, ¶¶ 41-101; Reply, Paper 26, at 2-13; Huck Dec. #2, ¶¶ 27-74.]
`
` Claims 1-7 and 10-17 would have been obvious over Link
`
`[Pet. Paper 2, at 36-46; Huck Dec. #1, GEN1002, ¶¶ 106-127; Reply, Paper 26, at 15-21; Huck Dec. #2, GEN1036, ¶¶ 75-92.]
`
` Claims 8-9 would have been obvious over Link and Nguyen
`
`[Pet., Paper 2, at 40-46; Huck Dec. #1, GEN1002, ¶¶ 116-127; Reply, Paper 26, at 20-21 Huck Dec. #2, GEN1036, ¶ 92.]
`
` RainDance has proffered no objective indicia of nonobviousness
`
`[Pet., Paper 2, at 46-51; Huck Dec #1, GEN1002, ¶¶ 128-138; Reply, Paper 26, at 21; Huck Dec. #2, ¶ 91.]
`
`Petitioner 10X Genomics
`
`2
`
`
`
`1. A method for droplet formation, the
`method comprising the steps of:
`
`providing a plurality of aqueous fluids each
`in its own aqueous fluid channel in fluid
`communication with one or more immiscible
`carrier fluid channels;
`
`forming droplets of aqueous fluid
`surrounded by an immiscible carrier fluid in
`the aqueous fluid channels;
`
`applying a same constant pressure to the
`carrier fluid in each of the immiscible carrier
`fluid channels; and
`
`adjusting pressure in one or more of the
`aqueous fluid channels, thereby to produce
`droplets of aqueous fluid in one or more
`outlet fluid channels.
`
`[‘430 patent, GEN1001, claim 1.]
`
`[‘430 patent, GEN1001, FIG. 1.]
`
`Petitioner 10X Genomics
`
`3
`
`
`
`[Pet., Paper 2, at 6-8; Huck Dec. #1, GEN1002, ¶¶ 15-18; Link, GEN1004, ¶¶ [0110], [0111],
`[0010], [0132], [0164]-[0166] , [0174].]
`
` Teaches applying constant pressure to carrier fluid
`streams flowing through carrier fluid channels and
`adjusting pressure to aqueous fluid flowing
`through an aqueous fluid channel to make droplets
`
` Droplets from inlet modules are in fluid
`communication within the same microfluidic device
`
` By controlling the pressure difference between the
`oil and water sources at the inlet module, the size
`and periodicity of the droplets generated [could]
`be regulated
`
` Recognized that certain droplet microfluidic
`applications require generating droplets of
`different sizes
`
`Petitioner 10X Genomics
`
`[Link, GEN1004, Fig. 2A.]
`
`[Link, GEN1004, Fig. 4.]
`
`4
`
`
`
`[Pet., Paper 2, at 6-8; Huck Dec. #1, GEN1002, ¶¶ 15-18; Link, GEN1004, ¶¶ [0110], [0111],
`[0010], [0132], [0164]-[0166] , [0174].]
`
` Teaches applying constant pressure to carrier fluid
`streams flowing through carrier fluid channels and
`adjusting pressure to aqueous fluid flowing
`through an aqueous fluid channel to make droplets
`
` Droplets from inlet modules are in fluid
`communication within the same microfluidic device
`
` By controlling the pressure difference between the
`oil and water sources at the inlet module, the size
`and periodicity of the droplets generated [could]
`be regulated
`
` Recognized that certain droplet microfluidic
`applications require generating droplets of
`different sizes
`
`Petitioner 10X Genomics
`
`[Link, GEN1004, Fig. 2A.]
`
`[Link, GEN1004, Fig. 4.]
`
`5
`
`
`
`[Pet., Paper 2, at 6-8; Huck Dec. #1, GEN1002, ¶¶ 15-18; Link, GEN1004, ¶¶ [0110], [0111],
`[0010], [0132], [0164]-[0166] , [0174].]
`
` Teaches applying constant pressure to carrier fluid
`streams flowing through carrier fluid channels and
`adjusting pressure to aqueous fluid flowing
`through an aqueous fluid channel to make droplets
`
` Droplets from inlet modules are in fluid
`communication within the same microfluidic device
`
` By controlling the pressure difference between the
`oil and water sources at the inlet module, the size
`and periodicity of the droplets generated [could]
`be regulated
`
` Recognized that certain droplet microfluidic
`applications require generating droplets of
`different sizes
`
`Petitioner 10X Genomics
`
`[Link, GEN1004, Fig. 2A.]
`
`[Link, GEN1004, Fig. 4.]
`
`6
`
`
`
`[Pet., Paper 2, at 6-8; Huck Dec. #1, GEN1002, ¶¶ 15-18; Link, GEN1004, ¶¶ [0110], [0111],
`[0010], [0132], [0164]-[0166] , [0174].]
`
` Teaches applying constant pressure to carrier fluid
`streams flowing through carrier fluid channels and
`adjusting pressure to aqueous fluid flowing
`through an aqueous fluid channel to make droplets
`
` Droplets from inlet modules are in fluid
`communication within the same microfluidic device
`
` By controlling the pressure difference between the
`oil and water sources at the inlet module, the size
`and periodicity of the droplets generated [could]
`be regulated
`
` Recognized that certain droplet microfluidic
`applications require generating droplets of
`different sizes
`
`Petitioner 10X Genomics
`
`[Link, GEN1004, Fig. 2A.]
`
`[Link, GEN1004, Fig. 4.]
`
`7
`
`
`
`Link anticipates claims 1-7
`and 12-17
`
`Petitioner 10X Genomics
`
`8
`
`
`
`[Pet., Paper 2, at 17-35; Huck Dec #1, GEN1002, ¶¶ 41-101; Reply, Paper 26, at 2-13; Huck Dec. #2, ¶¶ 27-74.]
`
`[Pet., Paper 2, at 27.]
`
`[Pet., Paper 2, at 27.]
`
`9
`
`Petitioner 10X Genomics
`
`
`
`[Pet., Paper 2, at 26-27; Huck Dec #1, GEN1002, ¶ 51; Decision Inst., Paper 13, at 6-7.]
`
`
`
`
`
`
`
`
`
`“Methods of forming such droplets”
` Producing “droplets of different size to allow for
`controlled droplet coalescence in the main channel.”
`“Methods for performing PCR in droplets”
`“Merging of droplets”
`“Interdigitation of sample droplets and PCR reagent
`droplets flowing through a channel”
`“Detection modules and methods of detecting
`amplification products in droplets”
`“Methods of releasing contents from the droplets”
`“Microfluidic chips for performing biological, chemical,
`and diagnostic assays”
`
`
`
`
`
`
`
`[‘430, GEN1001, 4:6-21.]
`
`[‘430, GEN1001, 7:36-38.]
`
`[‘430, GEN1001, 9:39-41.]
`
`[‘430, GEN1001, 9:55-59; 10:25-27.]
`
`[‘430, GEN1001, 10:9-11.]
`
`[‘430, GEN1001, 12:11-14.]
`
`[‘430, GEN1001, 14:24-28.]
`
`[‘430, GEN1001, 14:50-52.]
`
`Petitioner 10X Genomics
`
`10
`
`
`
`[Pet., Paper 2, at 17-35; Huck Dec #1, GEN1002, ¶¶ 41-101; Reply, Paper 26, at 2-13; Huck Dec. #2, ¶¶ 27-74.]
`
`1. A method for droplet formation, the
`method comprising the steps of:
`
`providing a plurality of aqueous fluids
`each in its own aqueous fluid channel in
`fluid communication with one or more
`immiscible carrier fluid channels;
`
`forming droplets of aqueous fluid
`surrounded by an immiscible carrier
`fluid in the aqueous fluid channels;
`
`applying a same constant pressure to
`the carrier fluid in each of the
`immiscible carrier fluid channels; and
`
`adjusting pressure in one or more of
`the aqueous fluid channels, thereby to
`produce droplets of aqueous fluid in
`one or more outlet fluid channels.
`
`[‘430 patent, GEN1001, claim 1.]
`
`Petitioner 10X Genomics
`
`Indisputably disclosed in
`Link
`
`[Reply, Paper 26, at 1; Decision to Inst., Paper 13, at 7.]
`
`Board:
`“Patent Owner does not dispute
`Petitioner’s
`contention
`that
`Link
`discloses the first two steps of claim 1 of
`the ’430 patent and the additional
`limitations of each of dependent claims
`2–7 and 12–17.”
`
`[Decision to Inst., Paper 13, at 7.]
`
`11
`
`
`
`[Pet., Paper 2, at 24-45; Huck Dec #1, GEN1002, ¶ 46; Reply, Paper 26, 4-8; Huck Dec. #2, GEN1036, ¶¶ 30-65.]
`
`Link:
`
`1. A method for droplet formation, the
`method comprising the steps of:
`
`providing a plurality of aqueous fluids
`each in its own aqueous fluid channel in
`fluid communication with one or more
`immiscible carrier fluid channels;
`
`forming droplets of aqueous fluid
`surrounded by an immiscible carrier fluid
`in the aqueous fluid channels;
`
`applying a same constant pressure to the
`carrier fluid in each of the immiscible
`carrier fluid channels; and
`
`adjusting pressure in one or more of the
`aqueous fluid channels, thereby to
`produce droplets of aqueous fluid in one
`or more outlet fluid channels.
`
`[‘430 patent, GEN1001, claim 1.]
`
`Petitioner 10X Genomics
`
`[Link, GEN1004, ¶ [0166]
`
`[Link, GEN1004, ¶ [0110]
`
`[Link, GEN1004, ¶ [0132]
`
`12
`
`
`
`[Pet., Paper 2, at 22-26; Huck Dec. #1, GEN1002, ¶¶ 47-50; Reply, Paper 26, at 8-10.; Huck Dec #2, GEN1036, ¶¶ 28-29, 66-68.]
`
`Link:
`
`[Link, GEN1004, ¶ [0174]
`
`[Link, GEN1004, ¶ [0166]
`
`“[T]he combination of [Link ¶¶ [0166] and [0173]-[0174]] would disclose
`a microfluidic system with multiple droplet-forming junctions and
`adjusting the pressure in the aqueous fluid channels….”
`
`[POR, Paper 21, at 37.]
`Link "does indeed disclose multiple droplet forming modules in the same
`device”
`
`[POR, Paper 21, at 3.]
`Link ¶ [0110] and Figure 1 "disclose systems with multiple inlet
`modules."
`
`[POR, Paper 21, at 21]
`13
`
`RainDance
`admits:
`
`Petitioner 10X Genomics
`
`
`
`[Pet., Paper 2, at 27-28; Huck Dec. #1, ¶ 42; Reply, Paper 26, at 1.]
`
`• Link provides extensive direction on how to use examples of
`microfluidic devices that a POSA would have viewed as consistent
`with the claimed methods.
`
`[Link, GEN1004, ¶¶[0086]-[0147], [0158]-[0270], [0316]-[0453]]
`
`• The microfluidic methods disclosed in Link were predictable
`because they contained no unusual components or methods.
`
`[Pet., Paper 2, at 28-29; Huck Dec. #1, GEN1002, ¶ 42.]
`
`• Link teaches methods of generating droplets using well-known
`droplet generating devices and technique.
`
`[Link, GEN1004, ¶¶[0131]-[0137], [0159]-[0166], [0173],
`[0174], [0179], Figs. 2A, 3, and 4.]]
`
`• A POSA would have had experience in performing similar
`microfluidic methods because the microfluidics field was mature
`and similar systems had been described previously.
`
`[GEN1005, 046501-9, Fig. 3(d); GEN1009, 2036:1-2, Fig. 3; GEN1015, 292:2, Fig. 5; GEN1011, 351:2-354:2, Figs. 2-4.]]
`
`Petitioner 10X Genomics
`
`14
`
`
`
`[POR, Paper 21, at 27]
`
`Link:
`
`Pressure-driven pumps
`
`or
`
`Positive-displacement pumps
`
`‘430 patent:
`
`Both pressure pumps and
`positive-displacement pumps
`work to control droplet size
`
`Petitioner 10X Genomics
`
`[Link, GEN1004, ¶ [0163-[0164].]
`
`[Link, GEN1004, ¶ [0165.]
`
`[‘430, GEN1001, 5:59-61.]
`
`[Pet., Paper 2, at 22-26; Huck Dec. #1, ¶¶ 31, 36, 46; Reply,
`Paper 26, at 4-5.; Huck Dec #2, GEN1036, ¶¶ 13-15]
`
`15
`
`
`
`[POR, Paper 21, at 16, 28-29.]
`
`Dr. Huck:
`
`“No claim of the '430 patent, however, requires that the same
`constant pressure be applied for any particular period of time.”
`[Huck Dec. #2, ¶ 20].
`
`Dr. Squires agrees:
`
`“Does Claim 1 require that
`Q:
`the same constant pressure be
`applied for any particular length of
`time?”
`
`A:
`
`“It does not….”
`[Squires depo, GEN1030, 79:1-16].]
`
`Q:
`
`“It’s not changing ever?”
`
`“Well, obviously, your turn
`A:
`it on and so before you turn it on,
`there is no pressure. If you want
`to adjust it, you can adjust it….”
`[Squires depo, GEN1030, 79:17-24].
`
`[Pet., Paper 2, at 22-26; Huck Dec. #1, ¶ 46; Reply, Paper 26, at 6-7.; Huck Dec #2, GEN1036, ¶¶ 19-21, 35-36]
`
`Petitioner 10X Genomics
`
`16
`
`
`
`[Pet., Paper 2, at 22-26; Huck Dec. #1, ¶ 46; Reply, Paper 26, at 6-7.; Huck Dec #2, GEN1036, ¶¶ 19-21, 35-36]
`
`Claim 8:
`
`Board:
`
`[‘430, GEN1001, claim 8.]
`
`“Dependent claim 8 recites ‘changing the pressure applied to
`the carrier fluid . . . based on the detecting step,’ demonstrating
`that ‘applying a same constant pressure to the carrier fluid’
`does not require that the pressure on the carrier fluid
`never be changed.”
`
`[Decision to Inst., Paper 13, at 11.]
`
`Petitioner 10X Genomics
`
`17
`
`
`
`[POR, at 1, 16-18, 47, 49, 52.]
`
`RainDance:
`The ‘430 patent uses “a common regulator for the flow of oil…”
`
`[POR, Paper 21, at 1.]
`The methods of the ‘430 patent would require “ripping out nearly half of the fluid
`regulators” of prior art devices
`
`[POR, Paper 21, at 49]
`
`Dr. Squires:
`
`“the one pressure source, your pressure regulator, is imposing the same pressure
`on all of the immiscible carrier fluid input channels….”
`
`[Squires depo, GEN1030, 53:22-54:12;.]
`
`those flow controls and hook all of those to a single … pressure
`“disconnect
`regulator….”
`
`[Squires depo, GEN1030, 54:25-56:20.]
`No reason to “hook it all up to one pressure regulator and apply the same constant
`pressure to everything….”
`
`[Squires depo, GEN1030, 61:10-62:23.]
`
`Petitioner 10X Genomics
`
`[Reply, Paper 26, at 7-8, 17-18; Huck Dec. #2, GEN1036, ¶¶ 37-44, 86-89.]
`
`18
`
`
`
`Only claims 3-4 recite a single pressure source
`
`[Pet., Paper 2, 30-31; Huck Dec. #1, GEN1002, ¶¶ 57-64; Reply, Paper 26, at
`7-8.; Huck Dec #2, GEN1036, ¶¶ 37-44, 72-73]
`
`[‘430, GEN1001, claims 3-4; Huck Dec. #2, GEN1036, ¶39.]
`
`[Huck Dec. #2, GEN1036, ¶¶40-
`44, 72-73.]
`
`Dr. Huck: Prior art devices used a single pressure source
`“The nozzle can be made from one or two oil
`lines providing
`constant flow of oil into the nozzle, a connection to the capillary tubing,
`and a connection to the storage well/reservoir (e.g. syringe).”
`[Link, GEN1004, ¶ [0132].]
`“The oil pressure in the circular reservoir is uniformly distributed
`…evenly infusing oil into channels via the symmetric inlet holes”
`[EX1032, 3186; see also Abstract, Fig. 2..]
`A “major advantage” to use a smaller number of regulators to provide
`liquids into the microfluidic device.
`
`Link:
`
`Zeng
`2010:
`Damean
`2009:
`
`Petitioner 10X Genomics
`
`[EX1033, 1712; see also Figs 1-2.]
`
`19
`
`
`
`[POR, Paper 21, at 10-11; 25.]
`
`Dr. Squires:
`the
`out
`carrying
`is
`Q
`So
`the
`to
`according
`calculations,
`mathematical model provided at Column
`6 of
`the '430 patent … necessary for
`practicing the '430 patent claims without
`undue experimentation?
`
`Let me think about
`A
`believe so….
`
`that.
`
`I
`
`[Squires depo, GEN1030, 72:14-73:9.]
`
`Dr. Link:
`claims
`the
`Do
`Q
`performing this calculation?
`
`require
`
`A
`
`No, they do not.
`[Link depo, GEN1037, 90:7-9.]
`
`Petitioner 10X Genomics
`
`[Reply, Paper 26, at 13-15.; Huck dec. #2, p. 17, ¶¶ 51-58]
`
`20
`
`
`
`[Reply, Paper 26, at 2-15; Huck dec. #2, ¶¶ 22-26]
`
`Element Not recited in Claim 1
`
`RainDance Citations Referencing the
`Element as part of the Invention
`
`Holding the carrier fluid pressure to a same constant
`pressure for an indefinite time period
`
`(not required by any claim)
`Designing a microfluidic device using the '430 patent's
`equations (Equations 1-16) to create channels with
`appropriate channel resistances
`
`• POR, Paper 21, at 16, 28-29
`• Squires Dec., EX2014, ¶¶ 50, 93,
`108
`
`• POR, Paper 21, at 53-54, 56
`• Squires Dec., EX2014, ¶¶ 91, 132
`
`(not required by any claim)
`Applying pressure from a single pressure source to
`each of the carrier fluid channels
`
`(only required by dependent claims 3 and 4)
`Controlling droplet size independently for each
`aqueous fluid
`
`(not required by any claim)
`
`Petitioner 10X Genomics
`
`• POR, Paper 21, at 1, 47, 49,
`• Squires Dec., EX2014, ¶¶ 63, 138
`
`• POR, Paper 21, at 8
`• Squires Dec., EX2014, ¶¶ 48, 65, 81,
`90, 97,
`
`[Huck dec. #2, ¶¶ 22-26, Table 1]
`
`21
`
`
`
`[Pet., Paper 2, at 28-36; Huck Dec. #1, GEN1002, ¶¶ 53-101 ; Reply, Paper 26, at 10-13; Huck Dec. #2,
`GEN1036, ¶¶ 69-74.]
`
`• Petition shows that Link discloses all the limitations of claims 1-7 and 12-17
`
`• Board instituted trial on, inter alia, anticipation of claims 1-7 and 12-17
`presented in Petition
`
`Board:
`
`“Patent Owner does not dispute Petitioner’s contention that Link
`discloses the first two steps of claim 1 of the ’430 patent and the
`additional limitations of each of dependent claims 2–7 and 12–17.”
`[Decision to Inst., Paper 13, at 7.]
`
`• RainDance POR only presents arguments for claims 2, 3, and 17
`
`• POR provides no separate arguments for claims 4-7 and 12-16
`
`Petitioner 10X Genomics
`
`22
`
`
`
`[Pet., Paper 2, at 28-36; Huck Dec. #1, GEN1002, ¶¶ 53-101 ; Reply, Paper 26, at 10-13; Huck Dec. #2, GEN1036, ¶¶ 69-74.]
`
`Claim
`2. The method of claim 1,
`wherein the same constant
`pressure derives from pressure
`in a reservoir in fluid
`communication with each of
`the carrier fluid channels.
`
`Exemplary Disclosure in Link
`“The nozzle can be made from one or
`two oil lines providing constant flow of
`oil into the nozzle, a connection to the
`capillary tubing, and a connection to
`the storage well/reservoir (e.g.
`syringe).” [¶0132]
`
`Link states that “[t]he pressure [of
`liquids] at the inlet module” can be
`regulated by “adjusting the pressure . .
`. with pressurized syringes feeding into
`those inlet channels.” [¶0166]
`
`Petitioner 10X Genomics
`
`23
`
`
`
`[Pet., Paper 2, at 28-36; Huck Dec. #1, GEN1002, ¶¶ 53-101 ; Reply, Paper 26, at 10-13; Huck Dec. #2, GEN1036, ¶¶ 69-74.]
`
`Claim
`3. The method of claim 1,
`wherein the same constant
`pressure is applied by a single
`pressure source to each of the
`carrier fluid channels.
`
`Exemplary Disclosure in Link
`“The nozzle can be made from one or
`two oil lines providing constant flow of
`oil into the nozzle, a connection to the
`capillary tubing, and a connection to
`the storage well/reservoir (e.g.
`syringe).” [¶0132]
`
`Petitioner 10X Genomics
`
`24
`
`
`
`[Pet., Paper 2, at 28-36; Huck Dec. #1, GEN1002, ¶¶ 53-101 ; Reply, Paper 26, at 10-13; Huck Dec. #2, GEN1036, ¶¶ 69-74.]
`
`Claim
`17. The method of claim 1,
`wherein said aqueous fluid
`channels comprise a plurality
`of microfluidic circuits, each of
`which comprises an
`independent aqueous fluid
`channel and wherein all
`members of said plurality of
`microfluidic circuits comprise a
`common immiscible carrier
`fluid channel.
`
`Exemplary Disclosure in Link
`“The analysis unit includes at least one
`inlet channel, at least one main channel
`… A plurality of analysis units of the
`invention may be combined in one
`device.” [¶0088]
`
`“Different sample inlet channels can
`communicate with the main channel at
`different inlet modules.” [¶0173]
`
`Petitioner 10X Genomics
`
`25
`
`
`
`[Pet., Paper 2, at 29-30; Huck Dec. #1, GEN1002, ¶¶ 53-56; Reply, Paper 26, at 10-
`12; Huck Dec. #2, GEN1036, ¶¶ 71-73.]
`
`Link:
`“The nozzle can be made from one or two oil lines providing constant flow of
`oil into the nozzle…and a connection to the storage well/reservoir (e.g.
`syringe).”
`
`[Link, GEN1004, ¶ [0132].]
`“The pressure at the inlet module can also be regulated by adjusting the
`pressure on the main and sample inlet channels,
`for example, with
`pressurized syringes feeding into those inlet channels.”
`
`[Link, GEN1004, ¶[0166].]
`
`Dr. Huck:
`“Link discloses using a pressurized syringe as a source for carrier fluid.”
`[Huck Dec. #2, ¶ 73.]
`
`Petitioner 10X Genomics
`
`26
`
`
`
`Claims 1-7 and 10-17 would
`
`have been obvious over Link
`
`Petitioner 10X Genomics
`
`27
`
`
`
`[Pet. Paper 2, at 36-46; Huck Dec. #1, GEN1002, ¶¶ 106-127; Reply, Paper 26, at 15-21; Huck Dec. #2, GEN1036, ¶¶ 75-92.]
`
`• POSA would have understood that regulating pressure is a results-
`effective variable
`• POSA would have considered cost/benefit during device design
`process
`• POSA would have arrived at claims 10-11 using routine optimization
`
`• Board: same rationale applies to claims 1-7 and 12-17
`
`“Based on the current record, we are persuaded that Petitioner’s reasoning and analysis regarding
`obviousness of claims 10 and 11 apply equally to the pressure limitations of claim 1 … We are
`therefore persuaded that Petitioner’s arguments and evidence regarding anticipation of claims 1–7 and
`12–17, together with its arguments and evidence regarding obviousness of claims 10 and 11, are
`sufficient to demonstrate a reasonable likelihood that … claims 1–7 and 12–17 of the ’430 patent
`would have been obvious to one of ordinary skill in the art in view of Link.”
`
`[Decision Inst., Paper 13, at 17.]
`
`Petitioner 10X Genomics
`
`28
`
`
`
`[Pet. Paper 2, at 37-40; Huck Dec. #1, GEN1002, ¶¶ 108-115; Huck Dec. #2, GEN1036, ¶ 90.]
`
`Dr. Squires agrees:
`“[A]ll of the variable discussed above in paragraphs 88 and 125
`[including pressure] are 'results-effective variables' for
`regulating droplet size.”
`
`[Squires Dec., EX2012, ¶ 128.]
`
`Board agrees:
`Petitioner’s evidence shows sufficiently that pressure is a results-
`effective variable for droplet size and that droplet size and
`periodicity can be controlled at each inlet by regulating the carrier
`fluid pressure and/or the aqueous fluid pressure …
`
`[Decision Inst., Paper 13, at 16.]
`
`Petitioner 10X Genomics
`
`29
`
`
`
`[Pet. Paper 2, at 37-40; Huck Dec. #1, GEN1002, ¶¶ 108-115; Reply, Paper 26, at 16-17; Huck
`Dec. #2, GEN1036, ¶¶ 63-65, 90.]
`
`Dr. Huck: factors chosen during design process v. device operation
`
`“[Y]ou have the channel geometry,
`because that doesn’t change during the
`experiment…you
`certain
`have
`a
`geometry
`certain material,
`or
`and
`probably certain fluids….”
`[Huck depo#1, EX2015, 117:6-15; Reply, Paper 26, at 16-17.]
`
`“In the design period of your experiment
`you can choose the channel width….”
`
`[Huck depo#2, EX2017, 353:18-20; Resp. Obs. on Cross, Paper ;40, at 12-13.]
`
`“[M]ost of the factors referenced by RainDance are set parameters that would
`not vary during the droplet formation process. For example, "viscosity of the fluids
`used," the "type of surfactants used," the "presence of reagents," the "nature of the
`buffers used," the "geometry of the system," the "type of nozzle used," and "the
`material used to construct the microfluidic channels" are all factors that would be
`chosen during the design process
`
`Petitioner 10X Genomics
`
`[Huck Dec. #2, GEN1036, ¶ 64.]
`
`30
`
`
`
`[Pet. Paper 2, at 37-40; Huck Dec. #1, GEN1002, ¶¶ 108-115; Huck Dec. #2, GEN1036, ¶ 90.]
`
`Dr. Link:
`
`Researchers sought “[t]o reduce overall system cost”
`
`Dr. Squires:
`
`“[C]omplex and costly microfluidic systems in the prior
`art.
`
`RainDance:
`
`“The use of pressure as the control variable offers
`additional benefits, including simplicity, reduced cost,
`and responsiveness….”
`
`[Reply, Paper 26, at 17; Link Dec., EX2014, ¶¶ 12-13; Squires Dec., EX2012, ¶47; POR, Paper 21, at 1, 5, 13, 18.]
`
`Petitioner 10X Genomics
`
`31
`
`
`
`[Pet. Paper 2, at 36-40; Huck Dec. #1, GEN1002, ¶¶ 107-115; Reply, Paper 26, at 17-19; Huck Dec. #2, GEN1036, ¶¶ 86-89.]
`
`RainDance:
`POR alleges no success “after ripping out nearly half of the fluid
`regulators”
`
`[POR, Paper 21, at 49; Squires depo., GEN1030, 54:25-56:20, 61:10-62:23; Reply, Paper 26, at 17-18; Huck Dec. #2, GEN1036, ¶¶ 86-89.]
`
`Dr. Huck: Prior art devices used a single pressure source
`“The nozzle can be made from one or two oil lines providing constant flow of
`[Huck Dec. #2, GEN1036, ¶¶40-44,
`72-73.]
`oil into the nozzle, a connection to the capillary tubing, and a connection to the
`storage well/reservoir (e.g. syringe).”
`
`Link:
`
`[Link, GEN1004, ¶ [0132].]
`
`Zeng
`2010:
`
`Damean
`2009:
`
`“The oil pressure in the circular reservoir is uniformly distributed …evenly
`infusing oil into channels via the symmetric inlet holes”
`
`[EX1032, 3186; see also Abstract, Fig. 2..]
`
`A “major advantage” to use a smaller number of regulators to provide liquids into
`the microfluidic device.
`
`Petitioner 10X Genomics
`
`[[EX1033, 1712; see also Figs 1-2.]
`
`32
`
`
`
`[Pet. Paper 2, at 36-40; Huck Dec. #1, GEN1002, ¶¶ 107-115; Reply, Paper 26, at 17-19; Huck Dec. #2, GEN1036, ¶¶ 86-89.]
`
`• Thorsen shows that droplet size can be controlled by adjusting
`aqueous pressure
`
`•
`
`‘430 claims do not require one to predict with certainty the exact
`droplet size droplet produced based on pressure difference
`
`[Thorsen, GEN1012, Fig. 4.]
`
`Petitioner 10X Genomics
`
`33
`
`
`
`[Reply, Paper 26, at 19-20; Huck Dec. #2, GEN1036, ¶¶ 83-85; POR, Paper 21, at 57-58.]
`
`• RainDance alleges that "constant flow of oil" taught in Link is
`incompatible with the "applying a same constant pressure" limitation
`in the '430 patent claims
`
`• RainDance provides no evidence showing that the Link reference
`criticized, discredited, or otherwise discouraged arriving at the
`claimed method
`• Link teaches “applying a same constant pressure” and teaches both
`pressure-driven pumps and positive-displacement pumps for
`controlling pressure
`• Link teaches towards the claimed methods, not away
`
`Petitioner 10X Genomics
`
`34
`
`
`
`[Pet. Paper 2, at 40-46; Huck Dec. #1, GEN1002, ¶¶ 116-127; Reply, Paper 26, at 20-21; Huck Dec. #2,
`GEN1036, ¶ 92.]
`
`8. The method of claim 7, further comprising
`the step of changing the pressure applied to
`the carrier fluid and/or the pressure applied to
`the one or more of the aqueous fluid channels
`based on the detecting step.
`[‘430, GEN1001, claims 8-9..]
`
`9. The method of claim 6, further comprising the step of
`changing the pressure applied to a first of the aqueous
`fluid channels based on the detecting step, thereby to
`change the size of the droplets in the first aqueous
`fluid channel and not in the other aqueous fluid
`channels.
`
`Nguyen:
`• A “detection system … for providing feedback
`signal to the droplet formation process”
`• An “optical system for evaluating parameters of
`the droplet formation process such as … droplet
`size.”
`• Methods for measuring droplet size and
`formation
`
`[Nguyen, GEN1006, 431.]
`
`Petitioner 10X Genomics
`
`[Nguyen, GEN1006, Fig. 4]
`
`35
`
`
`
`[Pet., Paper 2, at 46-51; Huck Dec #1, GEN1002, ¶¶ 128-138; Reply, Paper 26, at 21; Huck Dec. #2, ¶ 91; POR, Paper 21, 2.]
`
`• RainDance raised no objective indicia of nonobviousness
`during prosecution of ‘430 patent
`
`• Petition: no known evidence of objective indicia
`
`• RainDance POR provides a single, unsupported
`sentence referring to “long felt need” with no evidence or
`analysis
`
`Petitioner 10X Genomics
`
`36
`
`
`
`Lead Counsel
`Eldora L. Ellison
`(Reg. # 39,967)
`STERNE, KESSLER, GOLDSTEIN
`& FOX P.L.L.C.
`1100 New York Ave. NW
`Washington, DC 20005
`202.772.8508 (telephone)
`202.371.2540 (facsimile)
`eellison-PTAB@skgf.com
`
`Back-Up Counsel
`Deborah A. Sterling
`(Reg. # 62,732)
`STERNE, KESSLER, GOLDSTEIN
`& FOX P.L.L.C.
`1100 New York Ave. NW
`Washington, DC 20005
`202.772.8501 (telephone)
`202.371.2540 (facsimile)
`dsterlin-PTAB@skgf.com
`
`Back-Up Counsel
`David H. Holman
`(Reg. # 61,205)
`STERNE, KESSLER, GOLDSTEIN
`& FOX P.L.L.C.
`1100 New York Ave. NW
`Washington, DC 20005
`202.772.8989 (telephone)
`202.371.2540 (facsimile)
`dholman-PTAB@skgf.com
`
`Petitioner 10X Genomics
`
`4680861
`
`37
`
`
`
`CERTIFICATE OF SERVICE (37 C.F.R. § 42.6(e))
`
`The undersigned hereby certifies that the above-captioned 10X Genomics,
`
`
`
`
`
`Inc.'s Demonstratives were served in their entirety on September 21, 2016, upon the
`
`following parties via electronic mail:
`
`Derek C. Walter (Lead Counsel)
`Edward R. Reines (Back-Up Counsel)
`Adrian Percer (Back-Up Counsel)
`Elizabeth Weiswasser (Back-Up Counsel)
`WEIL, GOTSHAL & MANGES
`201 Redwood Shores Pkwy.
`Redwood Shores, CA 94065
`adrian.percer@weil.com
`edward.reines@weil.com
`derek.walter@weil.com
`elizabeth.weiswasser@weil.com
`RainDance10xService@weil.com
`
`
`
`
`
`
`
` STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
`
`/Eldora L. Ellison/
`
`
`
`
` Eldora L. Ellison, Ph.D. (Reg. No. 39,967)
`Date: September 21, 2016
` Lead Attorney for Petitioner 10X Genomics,
`
`
`
`
`
` Inc.
`
`
`
`
`
`1100 New York Avenue, N.W.
`Washington, D.C. 20005-3934
`(202) 371-2600
`
`
`
`4762859.1
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