IPR2015-01558
`Declaration of WILHELM T.S. Huck (Exhibit 1036)
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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`_____________________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`_____________________
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`10X GENOMICS, INC.
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`Petitioner
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`v.
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`RAINDANCE TECHNOLOGY, INC.
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`Patent Owner
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`
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`_____________________
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`Case IPR2015-01558
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`Patent 8,658,430
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`_____________________
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`SECOND DECLARATION OF WILHELM T.S. HUCK, Ph.D.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`TABLE OF CONTENTS
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`Introduction ...................................................................................................... 1
`I.
`Summary of Opinions ...................................................................................... 1
`II.
`III. My Background and Qualifications ................................................................. 2
`IV. List of Documents Considered in Formulating My Opinions ......................... 2
`V.
`Person of Ordinary Skill in the Art (POSA) .................................................... 5
`VI. Claim Construction .......................................................................................... 6
`A.
`Contrary to RainDance's arguments, the claims do not require a change in
`carrier fluid flow rate .................................................................................. 7
`1. Dr. Squires' logic regarding flow rate changes is flawed because the
`claims do not require using a particular type of pressure-regulator. .......... 8
`2. Dr. Squires' logic regarding flow rate changes is flawed because changes
`in aqueous flow do not always lead to changes in carrier fluid pressure ... 9
`RainDance incorrectly interprets "applying a same constant pressure" as
`including a time component .....................................................................10
`RainDance presents a flawed and incorrect view of how a POSA would
`understand the claimed method ................................................................13
`VII. RainDance has not rebutted that Link anticipates Claim 1 ...........................18
`A.
`RainDance does not dispute that Link teaches the microfluidic device of
`the '430 patent ...........................................................................................18
`RainDance has not rebutted my argument that Link teaches applying a
`"same constant pressure" to the carrier fluid: Link teaches this claim
`element ......................................................................................................19
`1. RainDance's arguments regarding application of a same constant pressure
`depend on an improperly narrow interpretation of the claims – the claims
`encompass the embodiments taught in Link ............................................22
`2. Application of a constant pressure would not have "gone against the
`conventional wisdom" ..............................................................................35
`3. The ability of other factors to affect droplet formation is irrelevant to and
`does not diminish Link's teaching a POSA to control droplet size by
`adjusting the pressure applied to the aqueous fluid channel ....................37
`
`B.
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`C.
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`B.
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`C.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`RainDance has not rebutted that Link teaches "adjusting pressure in one
`or more of the aqueous fluid channels" ....................................................39
`VIII. RainDance has not rebutted that Link discloses the limitations present in
`dependent claims ...........................................................................................41
`I maintain that Link teaches a reservoir or carrier fluid and therefore
`anticipates claim 2 ....................................................................................41
`I maintain that Link teaches using a single pressure source and therefore
`anticipates claim 3 ....................................................................................42
`I maintain that Link teaches a common immiscible carrier fluid channel
`and therefore anticipates claim 17 ............................................................44
`IX. RainDance has not rebutted that claims 1-7 and 10-17 would have been
`obvious in view of Link .................................................................................45
`Contrary to RainDance's assertions, pressure regulation presented a
`simple design choice to a POSA ..............................................................46
`Link did not teach away from the method of the '430 patent ...................48
`I maintain that a POSA would have had a reasonable expectation of
`success in performing the method of the '430 patent ...............................50
`RainDance does not dispute that pressure regulation is a results-effective
`variable .....................................................................................................52
`RainDance has not presented objective indicia of nonobviousness .........53
`RainDance does not present independent arguments regarding the
`obviousness of claims 8 and 9 in view of Link and Nguyen .........................53
`XI. Conclusion .....................................................................................................54
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`A.
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`B.
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`C.
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`A.
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`B.
`C.
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`D.
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`E.
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`X.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`
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`I, Wilhelm T.S. Huck, Ph.D., hereby declare as follows.
`I.
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`Introduction
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`1.
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`I am the same Wilhelm T.S. Huck who provided a previous
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`declaration in this proceeding (EX1002). My first declaration in this proceeding set
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`forth my opinions on the disclosures in the prior art and the understanding of a
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`person of ordinary skill in the art reading the disclosures in the prior art. I maintain
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`the same opinions today that were set forth in my first declaration.
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`2.
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`I am submitting this second declaration in reply to RainDance's
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`Response (Paper 21), the Declaration of Dr. Todd Squires (EX2012), and the
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`Declaration of Dr. Darren Link (EX2014).
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`II. Summary of Opinions
`After reviewing RainDance's Reply and the accompanying exhibits, I
`3.
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`maintain my opinion that every '430 patent claim is anticipated by or obvious over
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`the prior art. RainDance's arguments to the contrary are flawed because they are
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`dependent on a distorted view of the '430 patent that does not align with how a
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`POSA would have interpreted its claims. Because RainDance's analysis proceeds
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`from this skewed perspective, it offers no effective or substantive critiques of my
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`initial analysis. Further, I note that RainDance has not suggested any objective
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`indicia which might support its position.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`III. My Background and Qualifications
`4. My background and qualifications are detailed in ¶¶6-10 of my first
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`declaration, EX1002. My curriculum vitae has already been provided in this
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`proceeding as EX1003. In view of my experiences and expertise outlined in
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`EX1002 and EX1003, I am an expert in the fields of microfluidics and microscale
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`reactions and I was an expert in these fields before July 20, 2011. EX1002, ¶10.
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`IV. List of Documents Considered in Formulating My Opinions
`In formulating my opinions, I have considered all documents cited in
`5.
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`this declaration, including the documents in the chart below. I have further
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`considered all documents cited in RainDance's Response (Paper 21), Dr. Squires'
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`declaration (EX2012), and Dr. Link's declaration (EX2014).
`
`10X
`Genomics
`Exhibit #
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`Paper 2
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`Description
`
`Petition for Inter Partes Review of U.S. Patent No. 8,658,430, Case
`IPR2015-01558, Paper 2 (July 8, 2015)
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`Paper 13
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`Decision to Institute Inter Partes Review of U.S. Patent No.
`8,658,430, Case IPR2015-01558, Paper 13 (Jan. 19, 2016)
`
`Paper 21
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`RainDance Technologies, Inc.'s Patent Owner's Response to Petition
`for Inter Partes Review of U.S. Patent No. 8,658,430, Case
`IPR2015-01558, Paper 21 (April 25, 2016)
`
`1001
`
`
`
`Miller et al., "Manipulating Droplet Size," U.S. Patent No. 8,658,430
`B2 (filed on July 20, 2012; issued on February 25, 2014)
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`Link et al., "Microfluidic Devices and Methods of Use Thereof,"
`U.S. Patent Appl. Pub. No. 2008/0014589 (filed May 11, 2007;
`published January 17, 2008)
`
`Moscovici, M., et al., "Electrical Power Free, Low Dead Volume,
`Pressure-Driven
`Pumping
`for Microfluidic Applications,"
`Biomicrofluidics 4: 046501-1 to 046501-9 (2010)
`
`Nguyen, N., et al., "Optical Detection for Droplet Size Control in
`Microfluidic Droplet-Based Analysis Systems," Sensors and
`Actuators B 117: 431-436 (2006)
`
`Quake et al., "Microfabricated Crossflow Devices and Methods,"
`U.S. Patent Appl. Pub. No. 2002/0058332 (filed September 14, 2001;
`published May 16, 2002)
`
`File History for U.S. Patent No. 8,658,430
`
`Baroud, C., et al., "Dynamics of Microfluidic Droplets," Lab on a
`Chip 10: 2032-2-45 (May 21, 2010)
`
`Ismagilov et al., "Device and Method for Pressure-Driven Plug
`Transport and Reaction," U.S. Patent No. 7,129,091 (filed May 9,
`2003; issued October 31, 2006)
`
`Tan, Y., "Monodispersed Microfluidic Droplet Generation by Shear
`Focusing Microfluidic Device," Sensors and Actuators B 114: 350-
`356 (2006)
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`Thorsen, T., et al., "Dynamic Pattern Formation in a Vesicle-
`Generating Microfluidic Device," Phys. Rev. Lett. 86: 4163-4166
`(2001)
`
`Çengel, Y.A., et al., Fluid Mechanics: Fundamentals and
`Applications (McGraw-Hill) (2006)
`
`Top 10 Innovations 2014, THE SCIENTIST (Dec. 1, 2014),
`http://www.the-
`scientist.com/?articles.view/articleNo/41486/title/Top-10-
`Innovations-2014/, last accessed May 1, 2015
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`- 3 -
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`
`1004
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`1005
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`1006
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`1007
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`1008
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`1009
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`1010
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`1011
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`1012
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`1013
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`1014
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`

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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`Tan, Y., et al., "Design of Microfluidic Channel Geometries for the
`Control of Droplet Volume, Chemical Concentration, and Sorting,"
`Lab on a Chip 4: 292-298 (2004)
`
`Song, H., et al., "Reaction in Droplets in Microfluidic Channels,"
`Angew. Chem. Int. Ed. 45: 7336-7356 (2006)
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`Wang, K., et al., "DEP Actuated Nanoliter Droplet Dispensing Using
`Feedback Control," Lab on a Chip 9: 901-909 (2009)
`
`Deposition Transcript for Todd Squires, Thursday, June 2, 2016,
`Case IPR2015-01558
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`Li, W., et al., "Simultaneous generation of droplets with different
`dimensions in parallel integrated microfluidic droplet generators,"
`Soft Matter 4: 258-262 (2008)
`
`Zeng, Y., et al., "High-Performance Single Cell Genetic Analysis
`Using Microfluidic Emulsion Generator Arrays," Anal. Chem. 82:
`3183–3190 (2010)
`
`Damean, N., et al., "Simultaneous measurement of reactions in
`microdroplets filled by concentration gradients," Lab Chip 9: 1707–
`1713 (2009)
`
`Ward, T., et al., "Microfluidic flow focusing: Drop size and scaling
`in pressure versus flow-rate-driven pumping," Electrophoresis 26:
`3716–3724 (2005)
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`De Menech, M., et al., "Transition from squeezing to dripping in a
`microfluidic T-shaped junction," J. Fluid. Mech. 595:141-161 (2008)
`
`Deposition Transcript for Darren R. Link, Thursday, June 16, 2016,
`Case IPR2015-01558
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`Declaration of Todd Squires from IPR2015-00009
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`Annotated Figure 1 from U.S. Patent Appl. Pub. No. 2008/0014589
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`Declaration of Todd Squires
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`Declaration of Darren Link
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`- 4 -
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`1015
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`1016
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`1017
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`1030
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`1031
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`1032
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`1033
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`1034
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`1035
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`1037
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`1038
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`2011
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`2012
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`2014
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`Wilhelm Huck deposition transcript – April 13, 2016
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`
`2015
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`V. Person of Ordinary Skill in the Art (POSA)
`As stated in my previous declaration, I understand that a POSA in the
`6.
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`field of microfluidic devices and the methods of using such devices is a
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`hypothetical person who is presumed to be aware of all pertinent art, thinks along
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`conventional wisdom in the art, and is a person of ordinary creativity. EX1002,
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`¶12. Dr. Squires argues that the definition of a POSA as presented in my first
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`declaration "describes a person of extraordinary skill" because it references
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`knowledge of multiple fields. EX2012, ¶32. But I understand that a POSA in the
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`field of microfluidic devices would have had knowledge of the prior art in any
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`field so far as that knowledge relates to microfluidics. In my expert opinion, each
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`of the fields referenced in my definition of a POSA would have provided
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`significant teachings regarding the construction, operation, and potential uses of
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`microfluidic devices. Thus, a POSA would have had knowledge of (and been able
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`to research) the literature in each of those related fields, and Dr. Squires' definition
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`of a POSA is flawed because it attempts to minimize the significance of teachings
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`in those related fields.
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`7.
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`Dr. Squires' definition of a POSA is also flawed in that it presents the
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`negative limitation that a POSA "would not have been proficient" in the
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`"manipulation and control over droplet properties." Id. But the references cited in
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`my declarations show that the opposite is true—a POSA would have had
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`significant experience in forming and controlling the properties of droplets formed
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`in microfluidic devices. EX1002, ¶¶13-19; see also §§VII-IX below. I understand
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`that a review of the prior art literature illustrates what a POSA did know, and as
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`outlined in my declarations a POSA would have known of the methods claimed in
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`the '430 patent.
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`8.
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`Regardless of the flaws in Dr. Squires' analysis of a POSA, my
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`opinions would not change under the definition of a POSA as presented by Dr.
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`Squires.
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`VI. Claim Construction
`I understand that the Board has not provided a construction of any
`9.
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`term in its Institution Decision. I have reviewed RainDance's Response (Paper 21)
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`and Dr. Squires' declaration (EX2012), and note that neither offered a construction
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`of any specific term and neither objected to the Board's conclusion that it was not
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`necessary to provide any claim constructions. Thus, I understand that the claim
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`terms should be given their plain and ordinary meaning when interpreting the
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`claims. My original declaration was consistent with using the plain and ordinary
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`meaning of the claim language, and my testimony here applies that same standard.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`10. While RainDance has not offered a specific construction for any term,
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`it has argued for a specific interpretation of the '430 patent claims. I have addressed
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`these arguments below.
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`A. Contrary to RainDance's arguments, the claims do not require a change
`in carrier fluid flow rate
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`11. RainDance argued that "changing the flow rate of the carrier fluid is
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`necessarily part of the method of all claims of the '430 patent." EX2012, ¶¶70-71;
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`Paper 21, p15. I disagree with this sentiment, and agree with the Board's statement
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`that "the challenged claims do not recite changing the flow rate of the carrier
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`fluid." Paper 13, p12.
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`12. As I understand it, Dr. Squires' argument is that the claims of the '430
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`patent require (1) using "pressure-regulators" that drive carrier fluid with a
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`constant pressure while allowing flow rates to change (e.g., a pressurized gas
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`above the carrier fluid) and (2) changing the pressure applied to at least one
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`aqueous fluid channel. EX2012, ¶¶70-71, 50, 108. Based on this view of the
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`claims, Dr. Squires argues that the carrier fluid flow will necessarily change as part
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`of the claimed method because "changes to the pressure applied to an aqueous fluid
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`will affect the flow rate of the carrier fluid due to the coupling of the two fluids at
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`the junction." EX2012, ¶71. Dr. Squires' logic is flawed for at least two reasons.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`1. Dr. Squires' logic regarding flow rate changes is flawed because the
`claims do not require using a particular type of pressure-regulator.
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`13. Claim 1 requires application of "a same constant pressure," but claim
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`1 does not specify a type of pressure regulation that is to be used. Thus, the claims
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`cover methods using different types of pressure regulators. As Dr. Squires admitted
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`in his declaration, "[i]t was well known that there were multiple ways to introduce
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`fluid into microfluidic channels." EX2012, ¶41; EX1004, ¶[0109]. Within the
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`multiplicity of ways to introduce fluid, a POSA would have been aware of methods
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`that would be capable of delivering a constant pressure to a liquid in a microfluidic
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`device. I agree with Dr. Squires that those methods of applying constant pressure
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`included both positive-displacement pumping and pressurization of a gas above the
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`liquid (also known as a pressure-driven pump). EX2012, ¶¶42-43; EX1004,
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`¶¶[0165]-[0166]; EX1002, ¶¶44-46. The '430 patent states that both a pressure-
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`driven pump and a positive-displacement pump can successfully be used control
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`droplet formation. EX1001, 5:46-61. While the '430 patent states that pressure-
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`driven pumping gave "better control" of droplet size than positive-displacement
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`pumping, a POSA would not have understood pressure-driven pumping to be
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`required by the claims because (i) the claims don't recite any specific pressure
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`source, and (ii) the '430 patent demonstrated that positive-displacement also works.
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`Id.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`14. With either positive-displacement or pressure-driven pumping, a
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`POSA would have recognized that setting the control apparatus at a constant value
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`would provide a constant pressure absent other changes to the system. Pressure-
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`driven systems are designed to provide consistent pressure regardless of flow rate.
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`EX2012, ¶43. Positive-displacement pumps provide constant flow, which a POSA
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`would recognize as providing constant pressure absent changes to the system.
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`EX2012,¶¶41-43; EX1002, ¶31; EX1013, 330.
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`15. Positive-displacement pumps may alter their pressure output when
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`other changes to the system are made, but a POSA would have recognized that the
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`claims of the '430 patent allow for the pressure to change. For example, claim 8,
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`which depends from claim 1, includes a step of "changing the pressure applied to
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`the carrier fluid."
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`2. Dr. Squires' logic regarding flow rate changes is flawed because
`changes in aqueous flow do not always lead to changes in carrier
`fluid pressure
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`16. Dr. Squires' logic regarding the flow rate is also flawed because, even
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`if every claim required using the pressure-driven regulator that Dr. Squires
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`describes, changing the pressure applied to an aqueous fluid channel would not
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`necessarily lead to a change in carrier fluid flow rate. RainDance stated that I
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`agreed during deposition that adjustment of pressure necessarily results in a change
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`in flow rate. Paper 21, p15. That is not the case, as I only agreed that the aqueous
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`fluid channel pressure is "couple[d] to the oil channel" flow rate. EX2015, 177:18-
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`178:1. But I do not agree that such coupling necessarily leads to a change in carrier
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`fluid flow rate when aqueous pressure is changed.
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`17. Pressure can be changed in the aqueous fluid channels without
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`altering carrier fluid flow rate. For example, an operator might raise one aqueous
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`channel's pressure while lowering another aqueous channel's pressure in such a
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`way that there would be no net change in pressure transmitted to the carrier fluid
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`source. In this case, the carrier fluid flow would remain constant. EX1002, ¶¶49-
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`50; GEN1004, ¶[0166]; EX1007, ¶¶[0003], [0115].
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`18. Because, as described above, there are circumstances where carrier
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`fluid flow rate would not change when performing the claimed methods, a POSA
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`would not have understood the claims to necessarily include changing carrier fluid
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`flow rate.
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`B. RainDance incorrectly interprets "applying a same constant pressure"
`as including a time component
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`19. Dr. Squires and RainDance refer to "maintaining constant pressure on
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`an oil (carrier) channel" and "holding the pressure of all the oil channels to a same
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`constant value" as being part of the invention of the '430 patent. EX2012, ¶93;
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`Paper 21, p16. To the extent that such statements suggest that the claims of the '430
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`patent require the same pressure be used throughout the claimed method, and that
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`that pressure cannot be changed, I disagree.
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`20. Claim 1 of the '430 patent requires a same constant pressure be
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`applied to the carrier fluid entering the microfluidic device. No claim of the '430
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`patent, however, requires that the same constant pressure be applied for any
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`particular period of time. When Dr. Squires was asked about a time component, he
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`agreed that claim 1 "does not" require that the pressure be applied for any
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`particular length of time. EX1030, 79:1-8. Dr. Squires further explained that "if
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`you want to adjust [the pressure], you can adjust it" while performing the method
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`of claim 1:
`
`Q Does Claim 1 require that the same constant
`pressure be applied for any particular length of
`time?
`A It does not -- it says "constant," which
`connotes that it is not changing; but obviously, you
`turn it on when you start your experiment. So it went
`from zero to something. But it does not -- so same
`constant pressure to me connotes the pressure is not
`changing.
`You know, later, one -- if the drops overall
`are not the size that one wants, one can adjust that one
`same constant pressure, right. One can change that and
`set it at a different value if one decides, but the
`pressure on all of those carrier fluids imposed at the
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`inlet to all of those carrier fluids, it is the same
`pressure imposed at all of those; and it is constant,
`meaning it is, you know, it's not changing.
`Q It's not changing ever?
`A Well, obviously, you turn it on and so before
`you turn it on, there is no pressure. If you want to
`adjust it, you can adjust it; but in the normal
`operation of the device, basically you have your
`pressure regulator setting some pressure and that keeps
`the pressure constant. If the pressure regulator is
`doing what it's doing, that's what it does.
`
`EX1030, 79:1-24 (emphasis added).
`
`21.
`
`I agree that a POSA would have interpreted the claims as allowing the
`
`microfluidic device operator to change the pressure applied to carrier fluid because
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`this interpretation is consistent with language in the claims of the '430 patent. For
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`instance, no claim of the '430 patent references maintaining a pressure during any
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`particular portion of the claimed method. Claim 8 actually states the opposite,
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`requiring the carrier fluid and/or aqueous channel pressure be changed. EX1001,
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`16:49-52. I understand that because claim 8 depends from claim 1, claim 1
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`necessarily includes the limitations of claim 8. Therefore, a POSA would have
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`understood that claim 1 necessarily includes methods in which the operator makes
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`adjustments that lead to a change in the pressure applied to the carrier fluid.
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
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`C. RainDance presents a flawed and incorrect view of how a POSA would
`understand the claimed method
`
`22. RainDance's arguments for the patentability of the claims of the '430
`
`patent are based on the premise that I have "wholly misunderstood" the '430 patent
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`claims. I have reviewed RainDance's arguments, and I maintain my original
`
`opinions regarding the meaning of the '430 patent claims and their lack of
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`patentability over the art.
`
`23.
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`I understand that the proper standard for interpreting claims is to look
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`at the broadest reasonable interpretation of the claim language, in view of the
`
`specification. I also understand that the proper viewpoint in analyzing the claims is
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`to determine how a POSA would have viewed the claims. And I understand that it
`
`is improper to interpret the claims as containing elements described in the
`
`specification when those elements are not also recited in the claims.
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`24. RainDance's critiques of my arguments are flawed because those
`
`critiques are based on an interpretation of the claims that includes elements
`
`additional to those recited in the claims. RainDance has selectively cited passages
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`from the '430 passage specification and testimony from Dr. Link. EX2012, ¶¶48-
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`64; EX2014; Paper 21, pp. 8-14. I disagree with Dr. Link's interpretation of the
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`invention because his declaration presents only his opinion of the invention
`
`generally; he does not discuss the '430 patent claims. See, e.g., EX2014 ¶2-3. And
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`RainDance's arguments relate to multiple limitations that I only see in the '430
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`patent specification and not recited in the '430 patent claims. I disagree that
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`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
`
`RainDance's interpretation of the '430 patent claims is the same as the broadest
`
`reasonable interpretation of the claims. As a result of their artificially narrow
`
`presentation of the claimed method, Dr. Squires' and RainDance's analysis starts
`
`with a flawed premise and analyzes Link and the art from the wrong perspective.
`
`25. To illustrate, I have created Table 1 (shown below). Table 1 lists
`
`elements that RainDance referred to as being part of the '430 patent's "invention,"
`
`as well as elements from dependent claims that RainDance interpreted as being
`
`part of the claimed invention as a whole. For each element, I have cited to example
`
`portions of RainDance's Response and Dr. Squires' declaration that discuss that
`
`element as if it were part of every '430 patent claim.
`
`TABLE 1
`
`Element Not recited in
`Claim 1
`
`RainDance Citations Referencing the
`Element as part of the Invention
`
`Applying pressure from a
`single pressure source to
`each of the carrier fluid
`channels
`
`(only required by dependent
`claims 3 and 4)
`
`"[I]n the '430 patent, all of the droplet forming
`modules . . . share . . . a common regulator for the
`flow of oil . . . ." POR, p1.
`In describing "the invention of the '430 patent," Dr.
`Squires cites a passage in the '430 patent stating
`that "one regulator is used to drive and control the
`flow of immiscible fluid through the entire system."
`Squires Declaration, EX2012, ¶63
`"[A] cost/benefit analysis would have guided the
`skilled artisan away from the '430 patent and to a
`design option that Petitioner's expert never even
`mentions, which is to include, for each droplet-
`
`
`
`- 14 -
`
`

`
`
`
`Controlling droplet size
`independently for each
`aqueous fluid
`
`(not required by any claim)
`
`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
`
`forming junction, separate regulators for each oil
`and aqueous fluid channel." POR, p47.
`"[T]here remains a major gap between the passing
`disclosure in the Link reference of a 'pressure
`difference' and the notion that one could have a
`successful multi-junction system after ripping out
`nearly half of the fluid regulators." POR, p49.
`"Having a different syringe pump or pressure
`regulator at each carrier fluid channel goes directly
`invention.
`'430
`against
`the benefits of
`the
`Therefore, it is my opinion that a person of ordinary
`skill in the art would have found providing a
`different source of oil for every carrier fluid
`channel, as described and depicted in Link, would
`have taught away from the invention of the '430
`patent." Squires Declaration, EX2012, ¶138.
`
`"The claims of the '430 patent are directed to this
`novel technique for controlling droplet size in a
`plurality of fluidic circuits, wherein the same
`constant pressure is used to drive and control the
`flow of immiscible fluid through the entire system,
`and droplet size is independently controlled in each
`fluidic circuit by adjusting the pressure applied to
`the aqueous fluid channel." Squires Declaration,
`EX2012, ¶65.
`"In the claims of the '430 patent, the pressure
`applied to all of the carrier fluid channels in a
`system having a plurality of microfluidic circuits is
`held at a same constant pressure, while the pressure
`applied to the aqueous fluid channel in each circuit
`is independently adjusted to control droplet size."
`Squires Declaration, EX2012, ¶97.
`"The '430 patent, entitled 'Manipulating Droplet
`Size,' pertains to a method for independently
`controlling droplet size in a microfluidic device
`with multiple droplet-forming junctions." POR, p8.
`"The particular problem
`the
`inventors were
`
`
`
`- 15 -
`
`

`
`
`
`Holding the carrier fluid
`pressure to a same constant
`pressure for an indefinite
`time period
`
`(not required by any claim)
`
`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
`
`interested in was being able to independently
`manipulate the size of droplets at each of the
`junctions." Squires Declaration, EX2012, ¶48.
`"Nguyen does not disclose or otherwise discuss a
`microfluidic system with multiple junctions acting
`as distinct microfluidic circuits with independent
`control over droplet size as required by the '430
`patent." Squires Declaration, EX2012, ¶81.
`"Moreover, nothing in Link ¶ 166, or other
`paragraphs of Link, suggests that droplets of
`different aqueous fluids could be formed
`in
`separate inlet modules, with independent control
`over the size of droplets in each stream . . . ."
`Squires Declaration, EX2012, ¶90.
`
`"Further, Link ¶ 38 does not include any teaching
`of holding carrier fluid to a constant pressure while
`simultaneously adjusting the pressure in one or
`more aqueous fluid channels." POR, pp28-29.
`not
`"Link
`does
`describe
`independently
`manipulating droplet size in multiple aqueous
`channels by adjusting the pressure of the individual
`aqueous fluid channels while holding the pressure
`of all the oil channels to a 'same constant value.'"
`POR, p16 (emphasis original).
`"In other words, when holding the oil pressure
`constant, the oil flow rate can be adjusted strictly
`through adjustments to the aqueous pressure."
`Squires Declaration, EX2012, ¶50.
`"The invention described in
`'430 only works
`because maintaining constant pressure on an oil
`(carrier) channel, while changing the pressure on
`the aqueous (sample) channel, changes the flow
`rate of the oil." Squires Declaration, EX2012, ¶93
`(emphasis original).
`"Indeed, there is nothing in ¶ 38 that describes a
`system using multiple fluidic circuits, let alone that
`
`
`
`- 16 -
`
`

`
`
`
`Designing a microfluidic
`device using the '430 patent's
`equations (Equations 1-16)
`to create channels with
`appropriate channel
`resistances
`
`(not required by any claim)
`
`IPR2015-01558
`Declaration of WILHELM T.S. HUCK (Exhibit 1036)
`
`discusses holding the carrier fluids at a constant
`pressure while
`simultaneously adjusting
`the
`pressure in one or more of the aqueous fluid
`channels of the plurality of fluidic circuits."
`Squires Declaration, EX2012, ¶108.
`
`"Nothing in Link discloses such adjustments to the
`fluidic resistance of the aqueous and oil channels,
`nor the equations by which one may determine the
`proper design of multiple fluidic circuits operating
`with the same constant pressure applied to the
`carrier fluid, as required by the claims of the '430
`patent." Squires Declaration, EX2012, ¶91.
`"The '430 patent also provides a mathematical
`model by which a person of ordinary skill could
`tune such resistances, thereby allowing for granular
`control over the carrier fluid flow rate, and thus
`droplet volume, in different microfluidic systems
`which apply the same constant pressure to each of
`the carrier fluid channels. See id. 6:4-7:30. In
`comparison,
`there
`is no description
`in Link
`regarding the degree of influence that the aqueous
`pressure will have on the carrier fluid flow rate, let
`Squires
`alone
`a mathematical model."
`Declaration, EX2012, ¶132.
`"From here, the inventors recognized that the oil
`flow rate is coupled to the aqueous pressure and
`that, if the system is designed properly, this
`coupling could be harnessed to beneficial effect to
`control the oil flow rate and hence manipulate
`droplet size" POR, pp53-54.
`"This is because the coupling between circuits is
`only