UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`10X GENOMICS, INC.
`Petitioner
`
`v.
`
`RAINDANCE TECHNOLOGIES, INC.
`Patent Owner
`
`U.S. Patent No. 8,658,430 B2
`_____________________
`
`Inter Partes Review Case No. Unassigned
`_____________________
`
`DECLARATION OF WILHELM T.S. HUCK, Ph.D.
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`
`
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`

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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`
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`TABLE OF CONTENTS
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`I. 
`Overview .......................................................................................................... 1 
`Background and Qualifications ....................................................................... 3 
`II. 
`III.  List of Documents Considered in Formulating My Opinions ......................... 5 
`IV.  Person of Ordinary Skill in the Art (POSA) .................................................... 7 
`V. 
`State of the Art Before July 20, 2011 .............................................................. 8 
`VI.  The ’430 Patent and Its Claims ...................................................................... 13 
`VII.  Claim Construction ........................................................................................ 19 
`VIII.  Basis of My Opinions with Respect to Anticipation ..................................... 25 
`IX.  Ground 1: Link teaches every limitation of claims 1-7 and 12-
`17, arranged as claimed ................................................................................. 26 
`A. 
`Claim 1 ................................................................................................ 28 
`B. 
`Claim 2 ................................................................................................ 41 
`C. 
`Claim 3 ................................................................................................ 43 
`D. 
`Claim 4 ................................................................................................ 46 
`E. 
`Claim 5 ................................................................................................ 48 
`F. 
`Claim 6 ................................................................................................ 51 
`G. 
`Claim 7 ................................................................................................ 53 
`H. 
`Claim 12 .............................................................................................. 55 
`I. 
`Claim 13 .............................................................................................. 57 
`J. 
`Claim 14 .............................................................................................. 59 
`K. 
`Claim 15 .............................................................................................. 60 
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`Claim 16 .............................................................................................. 63 
`L. 
`M.  Claim 17 .............................................................................................. 65 
`Basis of My Opinions with Respect to Obviousness .................................... 69 
`X. 
`XI.  Ground 2: Comparison of claims 10-11 to Link ........................................... 71 
`A. 
`Claim 10 .............................................................................................. 72 
`B. 
`Claim 11 .............................................................................................. 76 
`XII.  Ground 3: Comparison of claims 8-9 to Link in view of Nguyen ................ 79 
`A. 
`Claim 8 ................................................................................................ 80 
`B. 
`Claim 9 ................................................................................................ 86 
`XIII.  Objective Indicia ............................................................................................ 90 
`A. 
`Commercial success ............................................................................ 91 
`B. 
`Long-felt but unmet need or failure of others ..................................... 92 
`C. 
`Industry praise ..................................................................................... 93 
`D.  Unexpectedly superior results ............................................................. 94 
`XIV.  Conclusion ..................................................................................................... 95 
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`
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`I, Wilhelm T.S. Huck, Ph.D., hereby declare as follows.
`
`I.
`
`0B0BOverview
`1.
`
`I am over the age of eighteen and otherwise competent to make this
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`declaration. I have been retained as an expert witness on behalf of 10X Genomics,
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`Inc. (“10X Genomics”) for the above-captioned inter partes review (“IPR”). I am
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`being compensated for my time in connection with this IPR at my standard legal
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`consulting rate, which is $400 per hour. I have no personal or financial interest in
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`the outcome of this proceeding.
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`2.
`
`I understand that the petition for inter partes review involves U.S.
`
`Patent No. 8,658,430 (“the ’430 patent”), GEN1001, which issued from U.S.
`
`Application No. 13/554,655 on February 25, 2014. I further understand that,
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`according to the USPTO records, the ’430 patent is currently assigned to
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`RainDance Technologies, Inc. (“Patent Owner”).
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`3.
`
`The face page of the ’430 patent cites a single related U.S. patent
`
`application. Specifically, the ’430 patent claims the benefit of U.S. Provisional
`
`Application No. 61/509,837 (“the ’837 application”), filed on July 20, 2011. I
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`understand that the ’430 patent is related to that application. I further understand
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`that, based on the filing date of the ’837 application, the earliest possible date to
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`which the ’430 patent may claim priority is July 20, 2011. I have been asked to
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`provide my analysis of the ’430 patent using an earliest filing date of July 20,
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`2011.
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`4.
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`In preparing this Declaration, I have reviewed the ’430 patent and
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`considered each of the documents cited herein, in light of general knowledge in the
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`art. In formulating my opinions, I have relied upon my experience, education, and
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`knowledge in the relevant art. In formulating my opinions, I have also considered
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`the viewpoint of a person of ordinary skill in the art (“POSA”) (i.e., a person of
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`ordinary skill in the field of microfluidics) before July 20, 2011.
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`5.
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`Broadly, this declaration presents my opinion that all ’430 patent
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`claims are anticipated by or obvious over the prior art. First, this declaration
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`presents my opinion that U.S. Patent App. Pub. No. US 2008/0014589 (“Link”)
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`(GEN1004) discloses and enables each and every limitation of claims 1-7 and 12-
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`17 of the ’430 patent, arranged as claimed. Second, this declaration presents my
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`opinion that a POSA would have had a reason to arrive at an embodiment within
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`the scope of claims 10 and 11 of the ’430 patent, with a reasonable expectation of
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`success, in view of Link and a POSA’s knowledge of the prior art. Third, this
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`declaration presents my opinion that a POSA would have had a reason to arrive at
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`an embodiment within the scope of claims 8 and 9 of the ’430 patent, with a
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`reasonable expectation of success, by combining the disclosures of Link and
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`Nguyen, N., et al., “Optical detection for droplet sized control in microfluidic
`
`droplet-based analysis systems,” Sensors and Actuators B 117: 431-436 (2006)
`
`(“Nguyen”) (GEN1006). Finally, this declaration describes how, in reaching my
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`conclusions regarding obviousness, I have considered potential objective indicia of
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`nonobviousness and concluded that there are none that I am aware of that would
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`support a claim of nonobviousness. The chart below summarizes the grounds of
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`unpatentability presented in this declaration.
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`Ground
`
`Basis
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`References
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`’430 Patent Claims
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`1
`
`2
`
`3
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`Anticipation
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`Obviousness
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`Link
`
`Link
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`Obviousness
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`Link in view of Nguyen
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`1-7 and 12-17
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`10-11
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`8-9
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`II.
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`1B1BBackground and Qualifications
`6. My qualifications and credentials are fully set forth in my curriculum
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`vitae, attached as GEN1003. I am an expert in the fields of microfluidics and
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`microscale reactions, and have been since 1999. Over the past 16 years, I have
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`accumulated significant training and experience in the fields of microfluidics,
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`microscale reactions, and other related fields. Accordingly, I am knowledgeable
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`about the experimental techniques and devices used in those fields.
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`7. My education includes receiving a M.Sc. in Chemistry from Leiden
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`University in the Netherlands in 1992. I also obtained a Ph.D. from Twente
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`University in the Netherlands in 1997. From 1997-1999, I was a postdoctoral
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`fellow at Harvard University working with Professor George M. Whitesides. From
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`1999 until 2012, I was a lecturer, reader, and professor at the University of
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`Cambridge where I taught and performed research in the Chemistry Department.
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`From 2004-2010, I was also the Director of the Melville Laboratory for Polymer
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`Synthesis at the University of Cambridge. Since 2010, I have been a Professor of
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`Physical Organic Chemistry at the Institute for Molecules and Materials at
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`Radboud University.
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`8.
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`In these positions, one focus of my research has been the study of how
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`cells sense their environment in microscale confinement. As part of that research, I
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`have developed microfluidics systems in which microdroplets are used as a tool for
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`studying complex reactions. I have used this technology to study differences
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`between individual cells at the transcriptional and metabolic level, as well as
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`interfacial reactions such as those that occur at oil-water interfaces.
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`9. My work has resulted in the publication of more than 225 papers, as
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`well as the grant of multiple patents on which I am listed as an inventor, including
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`patents for microfluidic systems. I have also founded and worked with
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`biotechnology companies that develop and use microfluidic systems, including
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`Sphere Fluidics and Cytofind Diagnostics. As a result of my expertise, I have
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`received numerous honors throughout my career. These honors include being given
`
`
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`a DuPont Young Professor Award, a Friedrich Wilhelm Bessel award from the
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`Humboldt Foundation, an ERC Advanced Grant, and a VICI award from the
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`Netherlands Organization for Scientific Research. I have also been named a Fellow
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`of the Royal Netherlands Academy of Arts and Sciences.
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`10. Accordingly, I am an expert in the fields of microfluidics and
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`microscale reactions, and have been since 1999. For that reason, I am qualified to
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`provide an opinion as to what a POSA would have understood, known or
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`concluded before July 20, 2011.
`
`III.
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`2B2BList of Documents Considered in Formulating My Opinions
`11.
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`In formulating my opinions, I have considered all documents cited in
`
`this declaration, including the documents in the chart below. In formulating my
`
`opinion, I have further considered U.S. Patent Nos. 7,129,091, 8,273,573,
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`8,304,193, 8,329,407, 8,889,083, and 8,822,148, as well as the file history for each
`
`of these patents.
`
`10X
`Genomics
`Exhibit #
`
`1001
`
`1004
`
`Description
`
`Miller et al., “Manipulating Droplet Size,” U.S. Patent No. 8,658,430
`B2 (filed on July 20, 2012; issued on February 25, 2014)
`
`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)
`
`
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`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)
`
`1005
`
`1006
`
`1007
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`1008
`
`File History for U.S. Patent No. 8,658,430
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`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
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`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)
`
`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
`
`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)
`
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`Song, H., et al., “Reaction in Droplets in Microfluidic Channels,”
`Angew. Chem. Int. Ed. 45: 7336-7356 (2006)
`
`Wang, K., et al., “DEP Actuated Nanoliter Droplet Dispensing Using
`Feedback Control,” Lab on a Chip 9: 901-909 (2009)
`
`1016
`
`1017
`
`
`
`IV.
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`3B3BPerson of Ordinary Skill in the Art (POSA)
`12.
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` I understand that a POSA is a hypothetical person who is presumed to
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`be aware of all pertinent art, thinks along conventional wisdom in the art, and is a
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`person of ordinary creativity. A POSA in the field of microfluidic devices and the
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`methods of using such devices would have had knowledge of the scientific
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`literature concerning microfluidic devices and the methods of using such devices
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`before July 20, 2011. A POSA would have had knowledge of strategies for
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`performing chemical and biological analysis in microfluidic devices. Typically, a
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`POSA would have had a Ph.D.
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`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. Alternately, a POSA could have had a
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`M.S. or bachelor’s degree in one of these disciplines with at least four or five years
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`of additional relevant experience, respectively. A POSA would have known how to
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`research the scientific literature in fields relating to microfluidics, including fluid
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`dynamics, microscale
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`reactions, chemistry, biochemistry, and mechanical
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`engineering. Also, a POSA may have worked as part of a multidisciplinary team
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`and drawn upon not only his or her own skills, but also taken advantage of certain
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`specialized skills of others in the team, e.g., to solve a given problem. For example,
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`a chemist, engineer, and a biologist may have been part of a team.
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`V.
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`4B4BState of the Art Before July 20, 2011
`13. Before July 20, 2011, the state of the art included the teachings
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`provided by the references discussed in this Declaration. Additionally, a POSA
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`would have been aware of other important references relating to microfluidic
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`droplet formation.
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`14. Generating droplets of aqueous fluids surrounded by an immiscible
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`carrier fluid was well-known in the art before July 20, 2011. For instance, Quake
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`developed a microfluidic device for analyzing biological materials, such as DNA,
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`in such droplets. (GEN1007, Abstract.) Quake’s system comprises flowing an
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`aqueous fluid through an inlet and into a unidirectional continuous flow of an
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`immiscible non-polar carrier fluid in a main channel. (GEN1007, ¶¶[0003], [0014]
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`[0015], [0070], [0100], [0125], [0287], [0290].) In Quake’s system, as the aqueous
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`fluid enters the main channel it is sheared off into droplets that are encapsulated by
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`the immiscible carrier fluid. (GEN1007, ¶¶[0015], [0070], [0125], [0287], [0290].)
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`Quake describes the inlet and main channels meeting at a T-shaped junction where
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`the droplets are formed. (GEN1007, ¶[0003], [0070], Fig. 16.) Quake further
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`describes that the droplet formation process is facilitated by “adjusting the pressure
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`of the oil and/or the aqueous solution, [so that] a pressure difference [is]
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`established between the two channels.” (GEN1007, ¶[0003].) Quake also notes
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`that, “[b]y controlling the pressure difference between the oil and water sources at
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`the droplet extrusion region, the size and periodicity of the droplets generated
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`[could] be regulated.” (GEN1004, ¶[0115].)
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`15. Following Quake, other researchers have developed microfluidic
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`systems that use pressure differences in the channels carrying aqueous fluid and
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`immiscible carrier fluid to generate aqueous fluid droplets surrounded by
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`immiscible carrier fluid. (GEN1004, ¶[0111], [0010], [0164]-[0166]; GEN1005,
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`046501-9, Fig. 3(d); GEN1009, 2036:1-2, Fig. 3; GEN1015, 292:2, Fig. 5;
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`1 One such system, disclosed by Link et al.,
`GEN1011, 351:2-354:2, Figs. 2-4.)0F0F
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`utilizes inlet modules where constant syringe-driven pressure drives both the flow
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`in an aqueous fluid channel and the flow in two immiscible carrier-fluid channels
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`1 Citations to patent literature provided as GEN10XX, Y:Z-Z indicate citations to
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`column Y, at lines Z-Z. For example, GEN10XX, 1:1-10 indicates column 1, lines
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`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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`Inter Parrtes Revieww of USPNN 8,658,4300 B2
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`Declaaration of WILHELMM T.S. HUUCK (Exhiibit GEN1
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`that inteersect withh the aqueoous fluid cchannel. (GGEN1004,
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`[0166].)) Link desscribes howw dropletss are formmed at the
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`164]-¶[0111], [0010], [01
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`junction oof the aquueous
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`fluid chhannel withh the carriier fluid chhannels. (GGEN1004,, ¶¶[0110], [0174], FFigs.
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`2A, 3, aand 4.) Figgures 2A off Link, repproduced bbelow, illusstrates the jjunction o
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`f the
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`aqueouss fluid chaannel with
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`the two ccarrier fluidd channelss that facillitates aquueous
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`droplet formation in an inlett module:
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`(GEN10004, Fig.
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`2A.) Figurre 4 of Liink, reprodduced beloow, clarifiies the drooplet
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`formatioon processs in Link’ss junction
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`by illustraating a cro
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`ss-sectionaal view of f that
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`Inter Parrtes Revieww of USPNN 8,658,4300 B2
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`Declaaration of WILHELMM T.S. HUUCK (Exhiibit GEN1
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`(GEN10004, Fig. 44.)
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`16. Link
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`describes
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`how, afteer droplets
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`are formeed at the jjunction off the
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`aqueouss and carrier fluid cchannels, thhose dropllets are caarried awaay in a disstinct
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`channell for colleection, anaalysis, or ffurther usee. (GEN10004, Fig.
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`1-4, ¶¶[00010],
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`both moddules
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`[0174].)) Link furtther teachees that muultiple dropplet-generaating moddules can bbe in
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`fluid coommunicattion within the samme microflluidic devvice, with
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`introduccing dropllets into a
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`common
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`main channnel compprising a fflow of caarrier
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`fluid. (GGEN1004,
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`¶¶[0173]-[0174], Figg. 2A and
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`1.)
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`7. Link
`1
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`further deescribes thaat, by “conntrolling thhe differencce betweenn the
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`oil and
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`water souurces at thee inlet moddule, the ssize and peeriodicity oof the dropplets
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`generateed [could]] be regullated.” (GEEN1004, ¶¶[0166].)
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`Reading LLink, a POOSA
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`would hhave been
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`was impportant to
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`aware thaat, when geenerating ddroplets inn microfluiidic devicees, it
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`generate ddroplets off uniform ssize. This
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`is becausee, for exammple,
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`uniformm size is neecessary inn droplet mmicrofluidi
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`c applicatiions that innvolve maaking
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`comparisons between reaction products in individual droplets. (GEN1004, ¶[0117];
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`GEN1015, 294:2.) A POSA would have been aware that uniform droplet size
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`makes comparison of droplets feasible because “uniform droplet size distributions
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`… reduce uncertainties associated with volume variations.” (GEN1015, 294:2.)
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`Further, by July 20, 2011, it was well-known that uniform droplet size was
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`“important in drug delivery, electrooptic device[], and catalysis” applications.
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`(GEN1016, 7350:1.) Finally, a POSA also would have been aware that uniform
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`droplets could be used “to study the self-assembly of gel emulsions and colloidal
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`particles
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`into
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`three-dimensional and periodic
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`two-dimensional structures.”
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`(GEN1016, 7350:1.)
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`18. But Link also teaches that other microfluidic droplet applications
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`require droplets of different sizes. (GEN1004, ¶[0129], [0157], [0450].) For
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`example, Link discloses using multiple inlet modules to each generate droplets of
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`different sizes, and directing those droplets into a main channel where droplets
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`could coalesce. (GEN1004, ¶¶[0010], [0198], Fig. 1.)
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`19. Given that a “droplet’s size and other properties are important for the
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`actual application [of droplet microfluidics],” Nguyen et al. developed, in 2006, a
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`“detection system … providing a feedback signal to the droplet formation
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`process.” (GEN1006, 431:2.) In Nguyen’s microfluidic device, laser light
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`scattering is used downstream of the droplet generation region to detect droplet
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`formation frequency, droplet size, and droplet shape. (GEN1006, 431:2, 432:2.)
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`Nguyen teaches that, after measuring these properties, a feedback signal can be
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`provided to control the droplet generation process. (GEN1006, 431:2, 436:1.) A
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`POSA would have known that feedback regulation was desirable because it was
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`well-known that “real-time feedback control … offer[ed] the promise of smart,
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`automated operation,” and that it allowed for “overcom[ing] 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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`VI.
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`5B5BThe ’430 Patent and Its Claims
`20.
`
`I understand that this declaration is being submitted together with a
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`petition for inter partes review of claims 1-17 of the ’430 patent. I have reviewed
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`the ’430 patent and, in assessing the ’430 patent, I have considered the teachings of
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`the scientific literature before July 20, 2011, in light of general knowledge in the
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`art as of that date. I understand that July 20, 2011, is the earliest date to which the
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`’430 patent may claim priority.
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`21. The ’430 patent is directed to “methods and systems for manipulating
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`droplet size.” (GEN1001, Abstract.) More specifically, it is directed to “methods
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`for manipulating droplet size that include forming droplets of aqueous fluid
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`surrounded by an immiscible carrier fluid, and manipulating droplet size during the
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`

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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`forming step by adjusting pressure exerted on the aqueous fluid or the carrier
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`fluid.” (Id.) The ’430 patent discloses performing these methods in microfluidic
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`devices that “include at least one substrate containing one or more etched or
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`molded channels.” (Id., 1:26-28.) The ’430 patent further discloses that one method
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`of forming droplets is by “flowing a stream of sample fluid so that the sample
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`stream intersects two opposing streams of flowing carrier fluid.” (Id., 2:36-38.)
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`Figure 1 of the ’430 patent, reproduced below, is illustrative of this process:
`
`22.
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`Independent claim 1 (the sole independent claim in the ’430 patent)
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`allows for “a plurality of aqueous fluids each in its own aqueous fluid channel,”
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`but also requires that each aqueous fluid be in “fluid communication” with the
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`carrier fluid. (Id., 16:22-24.) Claim 1 further states that “a same constant pressure”
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`is applied to “each of the immiscible carrier fluid channels . . . [while] adjusting
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`pressure in one or more of the aqueous fluid channels” to control droplet
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`formation. (Id., 16:27-31.) As a result of these adjustments, claim 1 states that the
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`device forms droplets of the aqueous fluids surrounded by the carrier fluid in an
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`aqueous fluid channel, and flows those droplets into an outlet channel located after
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`the junction of the aqueous fluid channel and the one or more carrier fluid
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`channels. (GEN1001, 16:25-26, 31-32.) To further clarify the claimed methods, I
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`have prepared a schematic that a POSA would have understood to illustrate a
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`method meeting the requirements of independent claim 1 of the ’430 patent. This
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`figure is based on the descriptions in the ’430 patent, including those cited above.
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`The figure is provided below, along with a key.
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`
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`- 15 -
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`

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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`
`
`
`
`23. The remaining claims in the ’430 patent are dependent claims. (Id.,
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`16:32-17:10.) These dependent claims can be grouped into a number of categories.
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`24. First, a number of claims add limitations relating to the type of
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`pressure applied to the carrier fluid. Claim 2 is dependent on claim 1, and requires
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`
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`- 16 -
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`that the pressure applied to the carrier fluid be “derived from pressure in a
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`reservoir in fluid communication with each of the carrier fluid channels.” (Id.,
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`16:32-34.) Claim 3 is dependent on claim 1, and requires that the pressure applied
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`to the carrier fluid be “applied by a single pressure source to each of the carrier
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`fluid channels.” (Id., 16:35-37.) Claim 4 is dependent on claim 3, and further
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`requires that the pressure source “comprises carrier oil.” (Id., 16:38-39.)
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`25. Some dependent claims add limitations relating to the size of the
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`droplets created. For instance, claim 5 depends from claim 1, and requires that
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`aqueous droplets made of a first and second aqueous fluid be “substantially
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`uniform in size.” (Id., 16:40-42.) In contrast, claim 6, which also depends from
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`claim 1, requires that “the droplets comprising a first aqueous fluid are a different
`
`size than the droplets comprising a second aqueous fluid.” (Id., 16:43-45.) Claim 7
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`depends from either claim 5 or claim 6, and adds the step of “detecting the size of
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`droplets.” (Id., 16:46-48.)
`
`26. A number of dependent claims add requirements that relate to
`
`changing the pressure applied to the aqueous fluid channels based on detecting the
`
`size of droplets in the aqueous fluid channels. The method of claim 8 depends from
`
`claim 7, and adds the step of “changing the pressure applied” to the carrier fluid, or
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`to at least one of the aqueous fluid channels based on detecting the size of droplets
`
`in the aqueous fluid channels. (Id., 16:49-52.) Claim 9 depends from claim 6, and
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`
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`

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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`requires changing the pressure in only one of the aqueous fluid channels to
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`selectively regulate the size of the droplets in that channel, based on detecting
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`droplet size. (Id., 16:53-57.)
`
`27. Claims 10 and 11 add limitations relating to regulating pressure in
`
`aqueous fluid channels. Claim 10 depends from claim 1, and requires that the
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`“pressure is not regulated in at least one of the aqueous carrier channels.” (Id.,
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`16:58-59.) Claim 11 also depends from claim 1, and requires that the “pressure is
`
`regulated in only one of the plurality of aqueous fluid channels.” (Id., 16:60-61.)
`
`28. Some dependent claims add limitations relating to the types of fluid
`
`used in the microfluidic device. Claim 12 depends from claim 1, and requires that
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`the immiscible carrier fluid be “an oil.” (Id., 16:62-63.) Claim 13 depends from
`
`claim 12, and further requires that the “oil comprises a surfactant. (Id., 16:64-65.)
`
`Claim 14 depends from claim 13, and further requires that “the surfactant is a
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`fluorosurfactant.” (Id., 16:66-67.) Claim 15 depends from claim 1, and requires
`
`that “the aqueous fluid comprises nucleic acid and reagents for conducting an
`
`amplification reaction.” (Id., 17:1-3.) Claim 16 depends from claim 15, and further
`
`requires that the amplification reaction be “a PCR reaction.” (Id., 17:4-5.)
`
`29. Finally, claim 17 requires that the microfluidic device be set up in a
`
`particular manner. Specifically, claim 17 requires that the device contain multiple
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`“microfluidic circuits, each of which comprises an independent aqueous fluid
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
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`channel.” (Id., 17:7-8.) Claim 17 further requires that the entire device be linked
`
`together by having a “common immiscible carrier fluid channel.” (Id., 17:9-10.)
`
`VII. 6B6BClaim Construction
`30.
`I understand that terms of the claims are to be given their broadest
`
`reasonable interpretations in light of the ’430 patent’s specification. I further
`
`understand that these terms should be given a meaning consistent with how they
`
`would be viewed by a POSA before July 20, 2011, and my analyses below are
`
`presented from such a viewpoint. Any term I have not expressly interpreted below,
`
`I have given its plain and ordinary meaning to a POSA before July 20, 2011.
`
`31. Applying a same constant pressure: Claim 1 requires “applying a
`
`same constant pressure to the carrier fluid in each of the immiscible carrier fluid
`
`channels.” (GEN1001, 16:27-28.) The ’430 patent does not describe any methods
`
`by which this requirement can be met, but a POSA would have understood that the
`
`flow rate of a fluid through a channel is a function of the pressure applied to the
`
`fluid. (GEN1013, 330.) Thus, a POSA would have understood that a fluid
`
`undergoing a constant flow would be driven by a constant pressure, and that a
`
`constant pressure would generate a constant flow. The ’430 patent states that
`
`“[a]ny pressure sources known in the art may be used with chips of the invention.”
`
`(GEN1001, 15:55-56.) A POSA would have been aware that known pressure
`
`
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`Inter Partes Review of USPN 8,658,430 B2
`Declaration of WILHELM T.S. HUCK (Exhibit GEN1002)
`
`
`sources included valves, pumps, and syringes. (See, e.g., GEN1004, ¶¶[0164]-
`
`[0166]; GEN1005, 046501-1.)
`
`32.
`
`I understand that an independent claim necessarily includes the scope
`
`of all claims that depend on that independent claim. Claim 3, which depends on
`
`claim 1, requires that the “same constant pressure is applied by a single pressure
`
`source.” (GEN1001, 16:35-38.) Therefore, a POSA would have understood that
`
`claim 1 encompasses at least applying a same constant pressure from a single
`
`pressure source. A POSA would have further understood that, because the pressure
`
`is applied from a single source to each carrier fluid channel, the pressure would be
`
`distributed equally across each carrier fluid channel to which the pressure is
`
`applied. Therefore, a POSA would have understood that the broadest reasonable
`
`interpretation of “applying a same constant pressure” encompasses at least
`
`generating a constant flow of carrier fluid in a carrier