UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
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`
`
`10X GENOMICS, INC.
`Petitioner
`v.
`RAINDANCE TECHNOLOGIES, INC.
`Patent Owner
`
`U.S. Patent No. 8,658,430 to Miller et al.
`Issue Date: February 25, 2014
`Title: Manipulating Droplet Size
`_____________________
`
`Inter Partes Review No. Unassigned
`_____________________
`
`Petition For Inter Partes Review of U.S. Patent No. 8,658,430 Under 35 U.S.C.
`§§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
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`
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
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`
`
`

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`
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`I. 
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`II. 
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`TABLE OF CONTENTS
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`Introduction ...................................................................................................... 1 
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`Grounds for standing and statement of the precise relief requested and
`the reasons therefor (37 C.F.R. § 42.104(a)-(b)) ............................................. 3 
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`III.  Overview .......................................................................................................... 3 
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`A. 
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`B. 
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`Person of ordinary skill in the art (“POSA”) and state of the art .......... 3 
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`The ’430 patent ...................................................................................... 8 
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`IV.  Claim construction ......................................................................................... 10 
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`V. 
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`Identification of challenge (37 C.F.R. § 42.104(b)) ...................................... 16 
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`A.  Ground 1: Claims 1-7 and 12-17 are anticipated by Link................... 17 
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`B. 
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`C. 
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`Ground 2: Claims 10 and 11 would have been obvious over Link ..... 36 
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`Ground 3: Claims 8 and 9 would have been obvious over Link in
`view of Nguyen ................................................................................... 40 
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`D.  Objective indicia do not support patentability .................................... 46 
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`VI.  Conclusion ..................................................................................................... 51 
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`VII.  Mandatory notices (37 C.F.R. § 42.8(a)(1)) .................................................. 51 
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`1
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`I.
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`Introduction
`10X Genomics, Inc.’s (“Petitioner”) Petition for Inter Partes Review
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`(“Petition”) seeks cancellation of claims 1-17 of U.S. Patent No. 8,658,430 (“the
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`’430 patent”) (GEN1001) as unpatentable under 35 U.S.C. §§ 102 and 103 in view
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`of the prior art.
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`The ’430 patent claims methods of forming droplets of aqueous fluid
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`surrounded by an immiscible carrier fluid in a plurality of aqueous fluid channels
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`in a microfluidic device by regulating the pressure applied to the aqueous fluid and
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`carrier fluid channels of the device. The ’430 patent also claims methods of
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`applying pressure to the channels of the device, as well as measuring the size of the
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`droplets generated in the device and then using those measurements to generate a
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`feedback loop to adjust droplet size. However, by July 20, 20111, the ’430 patent
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`claims were either anticipated or would have been obvious over the prior art.
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`For instance, claims 1-7 and 12-17, which require forming aqueous droplets
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`by adjusting the pressure applied to the aqueous channels of a device, were not
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`novel by July 2011. Indeed, U.S. Patent App. Pub. No. 2008/0014589 (“Link”)
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`(GEN1004) discussed below discloses as much. Moreover, adjusting the pressure
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`1 Petitioner does not concede that the ’430 patent is entitled to an effective filing
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`date of July 20, 2011, but it cannot be entitled to any earlier effective filing date.
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`1
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`applied to the aqueous channels of a device based on measurements of the size of
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`the droplets being generated in the channels, as required by claims 8 and 9, was
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`well-known in the art by July 2011, as evidenced by Nguyen, N., et al., “Optical
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`detection for droplet size control in microfluidic droplet-based analysis systems,”
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`Sensors and Actuators B 117: 431-436 (2006) (“Nguyen”) (GEN1006). And this
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`Petition demonstrates that a person of ordinary skill in the art (“POSA”) would
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`have had a reason to modify Link in view of Nguyen to control droplet uniformity,
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`which is desirable for certain droplet microfluidic applications. Furthermore, a
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`POSA would have had a reason to optimize the teachings of Link to arrive at
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`regulating the pressure in at least one or only one of the aqueous fluid channels, as
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`required by claims 10 and 11. This is because a POSA would have sought to
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`control droplet size by regulating the pressure applied to the channels of Link’s
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`microfluidic device.
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`Indeed, the ’430 patent claims are no more than a combination of these prior
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`art elements disclosed in Link and Nguyen that yields predictable results. As such,
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`it would have required no more than routine skill and knowledge in the art for a
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`POSA to successfully arrive at claims 8-11 of the ’430 patent in view of these
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`references. No objective
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`indicia of nonobviousness weighs
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`in favor of
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`patentability. Therefore, Inter Partes Review (“IPR”) is warranted.
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`2
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`II. Grounds for standing and statement of the precise relief requested and
`the reasons therefor (37 C.F.R. § 42.104(a)-(b))
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`Petitioner certifies that the ’430 patent is available for IPR and Petitioner is
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`not barred or estopped from requesting IPR of any of the challenged claims.
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`Petitioner requests that the Office institute IPR and cancel claims 1-17—all
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`claims—of the ’430 patent as unpatentable under 35 U.S.C. §§ 102 or 103.
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`Petitioner’s full statement of the reasons for the relief requested is set forth in
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`detail in § V.
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`III. Overview
`A.
`Person of ordinary skill in the art (“POSA”) and state of the art
`A POSA is a hypothetical person who is presumed to be aware of all
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`pertinent art, thinks along conventional wisdom in the art, and is a person of
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`ordinary creativity. A POSA in the field of microfluidic devices and the methods
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`of using such devices would have had knowledge of the scientific literature
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`concerning microfluidic devices and the methods of using such devices before July
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`20, 2011. (GEN1002, ¶12.) A POSA would have had knowledge of strategies for
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`performing chemical and biological analysis in microfluidic devices. (Id.)
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`Typically, a POSA would have had a Ph.D. in chemistry, biochemistry, mechanical
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`engineering, or a related discipline, with at least two years of experience in using,
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`designing or creating microfluidic devices. (Id.) Alternately, a POSA could have
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`had a M.S. or bachelor’s degree in one of these disciplines with at least four or five
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`3
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`years of additional relevant experience, respectively. (Id.) A POSA would have
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`known how to research the scientific literature in fields relating to microfluidics,
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`including fluid dynamics, microscale reactions, chemistry, biochemistry, and
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`mechanical engineering. (Id.) Also, a POSA may have worked as part of a
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`multidisciplinary team and drawn upon not only his or her own skills, but also
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`taken advantage of certain specialized skills of others in the team, e.g., to solve a
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`given problem. (Id.) For example, a chemist, engineer, and a biologist may have
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`been part of the team. (Id.) Before July 20, 2011, the state of the art included the
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`teachings provided by the references discussed in this Petition. Additionally, a
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`POSA would have been aware of other important references relating to
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`microfluidic droplet formation.
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`In 2000, Quake et al. developed a microfluidic system that sheared off
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`aqueous fluids into droplets surrounded by an immiscible fluid by flowing aqueous
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`fluids through one or more inlets and into a common main channel comprising a
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`unidirectional, continuous flow of the immiscible fluid. (GEN1007, ¶¶[0003],
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`[0014], [0015], [0100], [0125], [0290], [0287]; GEN1002, ¶14.) Quake’s droplets
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`were generated at a T-shaped junction formed between an inlet and the main
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`channel. (GEN1007, ¶[0003], Fig. 16; GEN1002, ¶14.) And by “adjusting the
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`pressure of the oil and/or the aqueous solution, a pressure difference [was]
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`established between the two channels” causing droplet formation. (GEN1007,
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`¶¶[0003], [0070]; GEN1002, ¶14.) Further, “[b]y controlling the pressure
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`difference between the oil and water sources at the droplet extrusion region, the
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`size and periodicity of the droplets generated [could] be regulated.” (GEN1004,
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`¶[0115]; GEN1002, ¶14.)
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`Following Quake, other similar microfluidic devices were developed that
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`used pressure differences between aqueous fluids flowing through inlet channels
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`and oils flowing through carrier fluid channels to make droplets of aqueous fluid
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`surrounded by an immiscible carrier fluid. (GEN1004, ¶[0111], [0010], [0164]-
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`[0166]; GEN1005, 046501-9, Fig. 3(d); GEN1009, 2036:1-2, Fig. 3; GEN1015,
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`292:2, Fig. 5; GEN1011, 351:2-354:2, Figs. 2-4; GEN1002, ¶15.)2 For example,
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`Link teaches applying constant pressure to carrier fluid streams flowing through
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`carrier fluid channels and to aqueous fluid flowing through an aqueous fluid
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`channel to make droplets. (GEN1004, ¶[0110], [0111], [0010], [0132], [0164]-
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`[0166]; GEN1002, ¶15.) These droplets are formed at the junction of the aqueous
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`2 Citations to patent literature provided as GEN10XX, YYY:Z-Z indicate citations
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`to column Y, at lines Z-Z. For example, GEN10XX, 1:1-10 indicates column 1,
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`lines 1-10. Citations to non-patent literature provided as GEN10XX, Y:Z indicate
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`citations to page number Y, at column number Z. For example, GEN10XX, 10:1
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`indicates p. 10, at column 1.
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`5
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`Petitionn for Interr Partes Reeview of UU.S. Patent
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`No. 8,6588,430
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`fluid chhannel withh the carrieer fluid chaannels. (GEEN1004, ¶¶¶[0010], [[0110], [01174],
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`Figs. 2AA, 3, and 44; GEN10002, ¶15.) FFigures 2AA and 4 of
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`Link, reprroduced beelow,
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`illustratte the juncction of thhe aqueouus fluid chhannel witth the twoo carrier ffluid
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`channells that facillitates formming aqueoous dropletts in the inllet modulee:
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`(GEN10004, Fig. 22A; GEN10002, ¶15.)
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`(GEN10004, Fig. 44 (illustratiing a cross
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`view of Fiig. 2A); GGEN1002, ¶¶15.)
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`The drooplets fromm various innlet modulles that aree in fluid coommunicaation withinn the
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`same mmicrofluidicc device wwere then fllowed throough the aqqueous flu
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`id channell and
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`into a
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`common mmain channnel compprising a fflow of c
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`arrier flui
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`d. (GEN1
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`¶¶[0173]-[0174], Fig. 2A and 1; GEN1002, ¶16.)
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`Link also recognized the importance of generating droplets of uniform size,
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`which is necessary in droplet microfluidic applications that, for example, involve
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`making comparisons between reaction products in individual droplets. (GEN1004,
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`¶[0117]; GEN1015, 294:2; GEN1002, ¶17.) Indeed, by July 2011, it was well-
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`known that generating droplets of uniform size was “important in drug delivery,
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`electrooptic device[], and catalysis” applications. (GEN1016, 7350:1; GEN1002,
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`¶17.) Further, it was well-known that uniform droplets could also be used “to study
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`the self-assembly of gel emulsions and colloidal particles into three-dimensional
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`and periodic two-dimensional structures.” (GEN1016, 7350:1; GEN1002, ¶17.)
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`And in terms of performing chemical reactions in droplets, “uniform droplet size
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`distributions … reduce[d] uncertainties associated with volume variations.”
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`(GEN1015, 294:2; GEN1002, ¶17.)
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`Like Quake, Link taught that by “controlling the pressure difference between
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`the oil and water sources at the inlet module, the size and periodicity of the
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`droplets generated [could] be regulated.” (GEN1004, ¶[0166]; GEN1002, ¶18.) In
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`addition, Link recognized that certain droplet microfluidic applications require
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`generating droplets of different sizes. (GEN1004, ¶[0129], [0450]; GEN1002,
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`¶18.) To that end, Link’s system utilized multiple inlet modules to generate
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`droplets of different sizes from each inlet module. (GEN1004, ¶[0010]; GEN1002,
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`7
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`¶18.) Link then directed the droplets of differing size into a main channel where
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`the droplets could coalesce to combine their contents. (GEN1004, ¶¶[0010],
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`[0198], Fig. 1; GEN1002, ¶18.)
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`Recognizing that a “droplet’s size and other properties are important for the
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`actual application [of droplet microfluidics],” in 2006, Nguyen et al. developed a
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`“detection system … providing a feedback signal to the droplet formation
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`process.” (GEN1006, 431:2; GEN1002, ¶19.) Nguyen’s system used laser light
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`scattering to detect droplet formation frequency, droplet size, and droplet shape
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`within a microfluidic device downstream of the droplet generation region.
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`(GEN1006, 431:2, 432:2; GEN1002, ¶19.) And upon measuring these parameters,
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`a feedback signal could be generated that would then control the droplet generation
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`process. (GEN1006, 431:2, 436:1; GEN1002, ¶19.) Further, it was well-known in
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`the art that “real-time feedback control … offer[ed] the promise of smart,
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`automated operation,” and that it allowed for “overc[oming] inherent performance
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`limits caused be irregularities in chip processing, surface contamination, and the
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`need to accommodate liquids of varied viscosity.” (GEN1017, 901:2, 908:1;
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`GEN1002, ¶19.)
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`B.
`The ’430 patent
`Against this backdrop, Miller et al. filed the patent application that issued as
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`the ’430 patent. (GEN1001.) The ’430 patent claims priority to July 20, 2011, and
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`8
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`is assigned to RainDance Technologies, Inc. (“Patent Owner”), according to the
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`Office’s electronic-assignment records.
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`The ’430 patent claims methods of generating droplets surrounded by an
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`immiscible carrier fluid in a microfluidic device. (GEN1001, 16:20-17:10;
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`GEN1002, ¶¶21-29.) The methods claimed in the ’430 patent recite providing
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`multiple aqueous fluids to a microfluidic device. (GEN1001, 16:22; GEN1002,
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`¶22.) Each aqueous fluid is contained within its own aqueous fluid channel that is
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`in fluid communication with one or more channels containing an immiscible
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`carrier fluid. (GEN1001, 16:22-24; GEN1002, ¶22, Fig. 1.) A constant pressure is
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`applied to the one or more carrier fluid channels, and the pressure is adjusted in
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`one or more of the aqueous fluid channels. (GEN1001, 16:27-30; GEN1002, ¶22.)
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`As a result of these pressure adjustments, droplets of the aqueous fluids surrounded
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`by the carrier fluid form in the aqueous fluid channel and flow into an outlet
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`channel that is located after the junction of the aqueous fluid channel and the one
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`or more carrier fluid channels. (GEN1001, 16:25-26, 30-31; GEN1002, ¶22, Fig.
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`1.) Figure 1 of the ’430 patent, reproduced below, is illustrative of this process:
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`9
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`(GEN1001, Fig. 1; GEN1002, ¶21, Fig. 1.)
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`IV. Claim construction
`In accordance with 37 C.F.R. § 42.100(b), the challenged claims must be
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`given their broadest reasonable interpretations in light of the specification of the
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`’430 patent. Terms not explicitly discussed below are plain on their face and
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`should be construed to have their ordinary and customary meanings.
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`Applying a same constant pressure: Claim 1 requires, inter alia, “applying
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`a same constant pressure to the carrier fluid in each of the immiscible carrier fluid
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`channels.” The ’430 patent does not describe any methods of “applying a same
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`constant pressure to the carrier fluid.” But a POSA would have understood that the
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`flow rate of a fluid through a channel is a function of the pressure applied to the
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`fluid. (GEN1013, p. 330; GEN1002, ¶31.) Thus, a POSA would have understood
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`that a fluid undergoing a constant flow would be driven by a constant pressure, and
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`that a constant pressure would generate a constant flow. (GEN1002, ¶31.)
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`10
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`Additionally, the ’430 patent states that “[a]ny pressure sources known in
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`the art may be used with chips of the invention.” (GEN1001, 15:55-56.) By July
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`2011 well-known pressure sources included valves, pumps, and syringes. (See,
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`e.g., GEN1004, ¶¶[0164]-[0166]; GEN1005, 046501-1; GEN1002, ¶31.) Claim 3,
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`which depends from claim 1, specifies that “the same constant pressure is applied
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`by a single pressure source.” (GEN1001, 16:35-37.) Thus, claim 1 encompasses at
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`least applying a same constant pressure from a single pressure source. See Dow
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`Chem. Co. v. United States, 226 F.3d 1334, 1341–42 (Fed. Cir. 2000) (concluding
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`that an independent claim should be given broader scope than a dependent claim to
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`avoid rendering the dependent claim redundant). And a POSA would have
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`understood that a constant pressure applied from a single source would be
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`distributed equally, i.e., the same, across all channels to which the pressure is
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`applied. (GEN1002, ¶32.)
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`As such, a POSA would understand
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`that
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`the broadest reasonable
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`interpretation of “applying a same constant pressure” encompasses at least
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`generating a constant flow of carrier fluid in a carrier fluid channel by applying
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`pressure from a single source, such as a syringe, wherein the pressure is distributed
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`equally across all channels to which the pressure is applied. (Id.)
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`Forming droplets of aqueous fluid … in the aqueous fluid channels:
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`Claim 1 requires, inter alia, “forming droplets of aqueous fluid … in the aqueous
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`11
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`fluid channels.” The ’430 patent states that “Fig. 1 shows an exemplary
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`embodiment of a device … for droplet formation.” And the droplet formation
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`device illustrated in Fig. 1 is discussed as follows:
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`Device 100 includes an inlet channel 101, and outlet channel 102, and
`two carrier fluid channels 103 and 104. Channels 101, 102, 103, and
`104 meet at a junction 105. Inlet channel 101 flows sample fluid to the
`junction 105. Carrier fluid channels 103 and 104 flow a carrier fluid
`that is immiscible with the sample fluid to the junction 105. Inlet
`channel 101 narrows at its distal portion wherein it connects to
`junction 105 (See FIG. 2). Inlet channel 101 is oriented to be
`perpendicular to carrier fluid channels 103 and 104. Droplets are
`formed as sample fluid flows from inlet channel 101 to junction
`105, where the sample fluid interacts with flowing carrier fluid
`provided to the junction 105 by carrier fluid channels 103 and
`104. Outlet channel 102 receives the droplets of sample fluid
`surrounded by carrier fluid.
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`(GEN1001, 4:22-36 (emphasis added), Fig. 1.) Further, the ’430 patent states that
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`“[t]he channels of each circuit [of the device] are configured such that they meet at
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`a junction so that droplets of aqueous fluid surrounded by carrier fluid are formed
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`at the junction….” (Id., 15:24-27.)
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`Thus, the ’430 patent specifies that droplets are formed at the junction of an
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`aqueous fluid channel and an immiscible carrier fluid channel. (GEN1002, ¶34.)
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`As such, a POSA would understand that the broadest reasonable interpretation of
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`“forming droplets of aqueous fluid … in the aqueous fluid channels” encompasses
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`forming droplets of aqueous fluid at the junction of an aqueous fluid channel and
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`an immiscible carrier fluid channel. (Id.)
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`Outlet fluid channel: Claim 1 requires, inter alia, “produc[ing] droplets of
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`aqueous fluid in one or more outlet fluid channels.” The ’430 patent states that
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`[t]he channels of each circuit [of the device] are configured such that
`they meet at a junction so that droplets of aqueous fluid surrounded by
`carrier fluid are formed at the junction an flow into the outlet channel.
`The outlet channel of each circuit is connected to a main channel that
`receives all of the droplets from the different fluidic circuits and flows
`the droplets to different modules in the chip for analysis.
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`(GEN1001, 15:24-31.) In addition, the ’430 patent points to Figure 1 of the ’430
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`patent when discussing the outlet fluid channel and the design of the ’430 patent’s
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`droplet forming device, stating that “[o]utlet channel 102 receives the droplets of
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`sample fluid surrounded by carrier fluid.” (Id., 4:35-36, Fig. 1.) As such, the
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`broadest reasonable interpretation of “outlet fluid channel” is the section of
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`channel placed after the junction of an aqueous fluid channel and an immiscible
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`carrier fluid channel that is connected to a main channel that receives droplets from
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`different fluidic circuits. (GEN1002, ¶35.)
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`Pressure in a reservoir: Claim 2 requires, inter alia, that the constant
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`pressure applied to the carrier fluid channel “derives from pressure in a reservoir in
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`fluid communication with each of the carrier fluid channels.” The ’430 patent
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`states that “[a]ny pressure sources known in the art may be used with chips of the
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`invention.” (Id., 15:55-56.) By July 2011, well-known pressure sources included
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`valves, pumps, and syringes. (See, e.g., GEN1004, ¶¶[0164]-[0166]; GEN1005,
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`046501-1; GEN1002, ¶36.) As such, a POSA would understand that the broadest
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`reasonable interpretation of “pressure in a reservoir” to encompass at least
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`applying pressure to a fluid using a valve, pump, or syringe. (GEN1002, ¶36.)
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`The detecting step: Claim 9 depends from claim 6, which depends from
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`claim 1, and requires “changing the pressure applied to a first of the aqueous
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`channels based on the detecting step.” The term “the detecting step” has no
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`antecedent basis in either claim 6 or claim 1. However, to the extent a POSA could
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`interpret the recitation of “the detecting step” referred to in claim 9, the broadest
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`reasonable interpretation would be that it requires detecting the size of droplets in
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`the microfluidic device. (GEN1002, ¶37.) This is because claim 7 recites
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`“detecting the size of droplets in one or more of the aqueous fluid channels.”
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`(GEN1001, 16:46-48; GEN1002, ¶37.) And the ’430 specification states that
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`“[m]ethods of the invention further involve measuring the size of a generated
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`droplet.” (GEN1001, 2:48-49; GEN1002, ¶37.)
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`Aqueous carrier channels: Claim 10 depends from claim 1 and requires
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`that the “pressure is not regulated in at least one of the aqueous carrier channels.”
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`The term “aqueous carrier channels” has no antecedent basis in claim 1. However,
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`because claim 1 recites the term “aqueous fluid channels,” a POSA would
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`understand claim 10 to require not regulating the pressure in at least one of the
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`aqueous fluid channels. (GEN1002, ¶38.)
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`Regulating pressure: Claims 10 and 11 require, inter alia, regulating the
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`pressure in at least one of the aqueous fluid channels and in only one of the
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`aqueous fluid channels, respectively. The ’430 patent does not specifically describe
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`any methods of regulating the pressure in at least one of the aqueous fluid channels
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`or in only one of the aqueous fluid channels. (Id., ¶39.) However, in discussing
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`regulating the pressure in the microchannels in general, the ’430 patent does so in
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`terms of discussing adjusting pressures in either the aqueous fluid channels or
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`immiscible carrier fluid channels to control droplet size, stating:
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`To control the volume of the aqueous droplet, within a range, droplet
`volume can be adjusted by tuning the oil infusion rate through the
`junction. This is readily achieved with a pressure regulator on the
`carrier fluid stream. In some cases it is desirable to have multiple
`junctions operating as separate circuits to generate droplets and have
`independent control over the oil infusion rates through each circuit.
`This is readily achieved by using separate pressure regulators for
`each aqueous stream and each carrier fluid stream. A simpler and
`lower cost system would have a single carrier oil source at a single
`pressure providing a flow of carrier oil through each system. The
`problem with such a system is that in adjusting the pressure to
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`regulate the flow of carrier oil in one circuit the carrier oil in all
`circuits would be effected and independent control over droplet
`volume would be compromised. Thus, it is important to have a
`means whereby at a fixed carrier oil pressure the flow of carrier
`oil in each of the circuits can be independently controlled to
`regulate droplet volume.
`
`(GEN1001, 1:59-2:10 (emphasis added).) Additionally, the ’430 patent states
`
`The invention recognizes that in a fluidic circuit, changing the
`pressure exerted on the aqueous phase changes the flow rate of the
`immiscible carrier fluid. Changing the flow rate of the immiscible
`fluid manipulates the size of the droplet. Thus, adjusting pressure,
`which changes flow rate, adjusts droplet size.
`
`(Id., 5:23-28 (emphasis added).) As such, a POSA would understand that the
`
`broadest reasonable interpretation of “regulating pressure” encompasses adjusting
`
`the pressure applied to either an aqueous fluid channel or immiscible fluid channel
`
`within a microfluidic circuit to change the flow rate, so as to adjust droplet size.
`
`(GEN1002, ¶39.)
`
`V.
`
`Identification of challenge (37 C.F.R. § 42.104(b))
`
`Petitioner requests IPR of claims 1-17—all claims—of the ’430 patent. Per
`
`37 C.F.R. § 42.6(c), copies of the references accompany the Petition. The Grounds
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`for unpatentability are further supported by the accompanying declaration of Dr.
`
`Wilhelm T.S. Huck, Ph.D. (GEN1002), an expert in the fields of microfluidics and
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`microscale reactions.
`
`Ground
`
`Basis
`
`Claims
`
`Index of References
`
`1
`
`2
`
`3
`
`§ 102(b) 1-7 and 12-17
`
`§ 103(a) 10 and 11
`
`Link
`
`Link
`
`§ 103(a) 8 and 9
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`Link in view of Nguyen
`
`A. Ground 1: Claims 1-7 and 12-17 are anticipated by Link
`As supported by the declaration of Dr. Huck, claims 1-7 and 12-17 are
`
`anticipated by U.S. Patent App. Pub. No. US 2008/0014589 (“Link”) (GEN1004).
`
`(GEN1002, ¶¶41-101.) Link published on January 17, 2008 and qualifies as prior
`
`art under 35 U.S.C. § 102(b) to the ’430 patent claims. As discussed below, and as
`
`confirmed by Dr. Huck, Link explicitly discloses every element of claims 1-7 and
`
`12-17, arranged as claimed and in a manner enabling to a POSA. (GEN1002, ¶¶41-
`
`101.)
`
`Independent claim 1 is anticipated by Link, as shown below:
`
`Claim 1
`A method for
`droplet formation,
`the method
`comprising the
`steps of:
`
`Link (GEN1004)
`“The present invention provides compositions and methods
`for forming sample droplet emulsions on a microfluidic
`substrate.” (¶[0131].)3
`
`“The present invention provides a method of pairing
`sample fluids to form a droplet or nanoreactor . . .”
`(¶[0010].)
`
`3 Emphasis added throughout, unless indicated otherwise.
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`Claim 1
`
`providing a
`plurality of
`aqueous fluids
`each in its own
`aqueous fluid
`channel in fluid
`communication
`with one or more
`immiscible carrier
`fluid channels;
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`Link (GEN1004)
`
`
`“Droplets of a sample fluid can be formed within the
`inlet module on the microfluidic device or droplets (or
`droplet libraries) can be formed before the sample fluid is
`introduced to the microfluidic device (‘off chip’ droplet
`formation).” (¶[0129].)
`“The present invention provides a method of pairing
`sample fluids to form a droplet or nanoreactor including,
`for example, (a) providing a microfluidic substrate
`including at least two inlet channels adapted to carry at
`least two dispersed phase sample fluids and at least one
`main channel adapted to carry at least one continuous
`phase fluid; (b) flowing a first sample fluid through a
`first inlet channel which is in fluid communication with
`the main channel at a junction, wherein the junction
`includes a first fluidic nozzle designed for flow focusing
`such that the first sample fluid forms a plurality of highly
`uniform, monodisperse droplets of a first size in the
`continuous phase; (c) flowing a second sample fluid
`through a second inlet channel which is in fluid
`communication with the main channel at a junction,
`wherein the junction includes a second fluidic nozzle
`designed for flow focusing such that the second sample
`fluid forms a plurality of highly uniform, monodisperse
`droplets of a second size in the continuous phase, wherein
`the size of the droplets of the second sample fluid are
`smaller than the size of the droplets of the first sample
`fluid….” (¶[0010].)
`
`“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].)
`
`“A ‘continuous’ fluidic stream is a fluidic stream that is
`produced as a single entity, e.g., if a continuous fluidic
`stream is produced from a channel, the fluidic stream, after
`production, appears to be contiguous with the channel
`outlet. The continuous fluidic stream is also referred to
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`Claim 1
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`Petition for Inter Partes Review of U.S. Patent No. 8,658,430
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`Link (GEN1004)
`as a continuous phase fluid or carrier fluid. The
`continuous fluidic stream may be laminar, or turbulent in
`some cases.” (¶[0111].)
`
`“Similarly, a ‘discontinuous’ fluidic stream is a fluidic
`stream that is not produced as a single entity. The
`discontinuous fluidic stream is also referred to as the
`dispersed phase fluid or sample fluid. A discontinuous
`fluidic stream may have the appearance of individual
`droplets, optionally surrounded by a second fluid. A
`‘droplet,’ as used herein, is an isolated portion of a first
`fluid that completely surrounded by a second fluid.”
`(¶[0112].)
`
`“The first and second fluids are immiscible with each
`other. For example, the discontinuous phase can be an
`aqueous solution and the continuous phase can a
`hydrophobic fluid such as an oil.” (¶[0114].)
`
`“The fluid passing through the main channel and in
`which the droplets are formed is one that is immiscible
`with the droplet forming fluid. The fluid passing through
`the main channel can be a non-polar solvent, decane (e g.,
`tetradecane or hexadecane), fluorocarbon oil, silicone oil or
`another oil (for example, mineral oil).” (¶[0118].)
`
`“The microfluidic device of the present invention includes
`one or more inlet modules. An ‘inlet module’ is an area of a
`microfluidic substrate device that receives molecules, cells,
`small molecules or particles for additional coalescence,
`detection and/or sorting. The inlet module can contain one
`or more inlet channels, wells or reservoirs, openings, and
`other features which facilitate the entry of molecules, cells,
`small molecules or particles into the substrate. A substrate
`may contain more than one inlet module if desired.
`Different sample inlet channels can communicate with
`the main channel at different inlet modules. Alternately,
`different sample inlet channels can communication [sic]
`with the main channel at the same inlet module. The
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`Claim 1
`
`forming droplets of
`aqueous fluid
`surrounded by an
`immiscible carrier
`fluid in the
`aqueous fluid
`channels;
`
`Link (GEN1004)
`inlet module is in fluid communication with the main
`channel. The inlet module generally comprises a
`junction between the sample inlet channel and the main
`channel such that a solution of a sample (i.e., a fluid
`containing a sample such as molecules, cells, small
`molecules (organic or inorganic) or particles) is introduced
`to the main channel and forms a plurality of drop