`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`THERMO FISHER SCIENTIFIC INC.,
`Petitioner,
`
`v.
`
`THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
`Patent Owner
`
`_____________________
`
`Case: IPR2018-01369
`U.S. Patent No. 8,110,673
`_____________________
`
`DECLARATION OF KIRK S. SCHANZE, Ph.D.
`
`
`
`
`
`
`TFS1002
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`TABLE OF CONTENTS
`
`I. 
`II. 
`III. 
`IV. 
`V. 
`
`VI. 
`
`Overview ....................................................................................................... 1 
`My background and qualifications ............................................................... 1 
`Basis for my opinion ..................................................................................... 3 
`Person of ordinary skill in the art ................................................................. 9 
`State of the art before January 31, 2005 ..................................................... 11 
`A.  Conjugated polymers and their properties were well known
`by 2005 ................................................................................................ 11 
`B.  Adaption of conjugated polymers for use in biosensing
`systems ................................................................................................ 15 
`C.  Systems having two different optically active units in a
`conjugated polymer were common by 2005 ....................................... 21 
`D.  By 2005, the field understood that inter-chain energy
`transfer in conjugated polymers is the most efficient
`pathway for energy transfer ................................................................. 22 
`The ’673 patent and its claims .................................................................... 27 
`A. 
`Independent claim 1 ............................................................................ 32 
`B.  Dependent claims 2, 3, 6-12, 14-17 and 19 ......................................... 33 
`VII.  Meaning of claim terms .............................................................................. 33 
`VIII.  The basis of my analysis with respect to obviousness ............................... 36 
`Claims 1, 3, 7-12, 14-17 and 19 would have been obvious over Hou
`IX. 
`and Inganas ................................................................................................. 38 
`A.  Claim 1 ................................................................................................ 38 
`A POSA would have had a reason to combine Hou
`1. 
`and Inganas .............................................................................. 56 
`A POSA would have had a reason to use Hou's
`a) 
`copolymers in Inganas' system ...................................... 56 
`Although Hou's polymer was developed for use
`in LEDs, its usefulness as a biosensor would
`have been apparent ........................................................ 62 
`It would have been obvious to solubilize Hou's
`copolymer for use as a biosensor ................................... 62 
`A POSA would have had a reasonable expectation of
`success at arriving at the claimed aggregation sensor ............. 63 
`
`b) 
`
`c) 
`
`2. 
`
`
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`- i -
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`

`

`a) 
`
`b) 
`
`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`It would have been
`routine
`to append
`zwitterionic side-chains onto Hou's copolymers ........... 63 
`A POSA would have expected to be able to use
`Hou's solubilized copolymer as an aggregation
`sensor ............................................................................. 66 
`B.  Claim 3 ................................................................................................ 69 
`C.  Claims 7-12 and 14.............................................................................. 71 
`D.  Claims 15, 16 and 19 ........................................................................... 78 
`E.  Claim 17 .............................................................................................. 81 
`Claims 1, 2 and 6 would have been obvious over Hou, Bazan and the
`Molecular Probes Handbook ...................................................................... 83 
`A.  Claim 1 ................................................................................................ 84 
`A POSA would have had a reason to combine Hou,
`1. 
`Bazan, and the Handbook ........................................................ 94 
`A POSA would have had a reasonable expectation of
`success at arriving at the claimed aggregation sensor ............. 99 
`B.  Claim 2 ..............................................................................................101 
`C.  Claim 6 ..............................................................................................105 
`Patent Owner's potential evidence of objective
`indicia of
`nonobviousnsess does not change my opinion regarding
`the
`obviousness of the challenged claims ....................................................... 108 
`
`2. 
`
`X. 
`
`XI. 
`
`
`
`
`
`- ii -
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`I, Kirk S. Schanze, do hereby declare as follows:
`
`Overview
`1.
`
`I am over the age of 18 and otherwise competent to make this
`
`
`I.
`
`declaration. I have been retained as an expert on behalf of Thermo Fisher
`
`Scientific Inc. (“Thermo Fisher”). I understand this declaration is being submitted
`
`together with a petition for Inter Partes Review (“IPR”) of claims 1-3, 6-12, 14-
`
`17, and 19 of U.S. Patent No. 8,110,673 (“the ’673 patent”) (TFS1001).
`
`2.
`
`I am being compensated for my time in connection with this IPR at
`
`my standard legal consultant rate of $375/hr. I have no personal or financial
`
`interest in Thermo Fisher or in the outcome of this proceeding.
`
`3.
`
`In preparing this declaration, I have reviewed the ’673 patent
`
`(TFS1001) and considered each of the documents cited therein, in light of the
`
`general knowledge in the art before January 31, 2005. I have also relied upon my
`
`experience in the relevant art and considered the viewpoint of a person of
`
`ordinary skill in the art (“POSA”; defined in § IV) before January 31, 2005.
`
`II. My background and qualifications
`4.
`I am currently the Robert A. Welch Distinguished University Chair in
`
`the Chemistry Department at the University of Texas, San Antonio. A copy of
`
`my CV is attached as Exhibit TFS1027.
`
`5.
`
`I earned by B.S. in Chemistry from Florida State University in 1979
`
`and my Ph.D. in Organic Chemistry from the University of North Carolina,
`
`
`
`- 1 -
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`Chapel Hill, in 1983. I was a Postdoctoral Research Associate in the Department
`
`of Chemistry at the University of North Carolina, Chapel Hill from 1983-1984. I
`
`was then a Miller Postdoctoral Fellow in the Chemistry Department of the
`
`University of California, Berkeley from 1984-1986.
`
`6.
`
`In 1986 I was appointed an Assistant Professor in the Department of
`
`Chemistry of the University of Florida. I became an Associate Professor at
`
`Florida in 1992 and was appointed full Professor in 1997. From 1997 to 2016 I
`
`held various Professorship chairs as outlined in my CV. In 2016 I moved to my
`
`current position at the University of Texas, San Antonio, where I serve as the
`
`Welch Distinguished Professor.
`
`7. Throughout my career I have earned various honors and awards,
`
`including the Globalization Award from American Chemical Society (ACS) in
`
`2018. I was made a Fellow of the ACS in 2011, and won the Florida Award from
`
`the Florida Section of ACS in 2009. I have also been awarded many Visiting
`
`Professor and Lecturer appointments at various universities throughout Asia. A
`
`full list of my Honors and Awards is provided in my CV.
`
`8.
`
`I have also held many professional service positions, such as the Chair
`
`of the Editor Search Committee for the ACS in 2014 and 2015 and I was the
`
`Chair of the ACS Publications Editors Conference in San Diego in 2016. I was
`
`Associate Editor of the American Chemical Society (ACS) Journal Langmuir
`
`
`
`- 2 -
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`from 2000 – 2008. Since 2008 I have served as founding Editor in Chief (EIC) of
`
`ACS Applied Materials & Interfaces. This is one of the largest technical journals
`
`in the field of materials chemistry and materials science. As EIC, I overview the
`
`review of more than 20,000 papers that are submitted annually for consideration
`
`to be published.
`
`9.
`
` My research primarily focuses on work in the fields of conjugated
`
`polymers,
`
`luminescence
`
`imaging, photochemistry and photophysics and
`
`photoresponsive materials. I have been conducting research on conjugated
`
`polymers, luminescence imaging and photoresponsive materials since at least
`
`1986. As such, as of January 2005 I met the qualifications for a person of
`
`ordinary skill in the art (POSA) as defined below, and I am qualified to opine on
`
`what the opinion of a POSA would have been at that time.
`
`III. Basis for my opinion
`10. In formulating my opinion, I have considered all documents cited
`
`herein, including the following:
`
`Thermo
`Fisher
`Exhibit #
`
`1001
`
`1003
`
`Description
`
`Bazan et al., “Aggregation Sensor and Solutions and Kits
`Comprising The Same,” U.S. Patent No. 8,110,673 (filed
`February 23, 2010; issued February 7, 2012)
`Yang, J., et al., “High-Efficiency Saturated Red Emitting
`Polymers Derived from Fluorene and Naphthoselenadiazole,”
`Macromolecules 37: 1211-1218 (2004)
`
`
`
`- 3 -
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`
`Thermo
`Fisher
`Exhibit #
`
`Description
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`Wang, S., et al., “Size-Specific Interactions Between Single- and
`Double-Stranded Oligonucleotides and Cationic Water-Soluble
`Oligofluorenes,” Adv. Funct. Mater. 13:463-467 (2003)
`Haugland, R., “1.2 – Kits for Labeling Proteins and Nucleic
`Acids” and “1.3 – Alexa Fluor Dyes: Simply the Best” in
`Handbook of Fluorescent Probes and Research Products, 9th
`Ed., Molecular Probes, Inc. (2002)
`Inganas, et al., “Polyelectrolyte Complex (e.g. Zwitterionic
`Polythiophenes) with a Receptor (e.g. Polynucleotide, Antibody
`etc.) for Biosensor Applications,” International Patent
`Application Publication No. WO 03/096016 A1 (filed May 8,
`2003; published November 20, 2003)
`Hou, Q., et al., “Novel red-emitting fluorene-based copolymers,”
`J. Mater. Chem., 12: 2887-2892 (2002)
`File History for U.S. Patent No. 8,110,673, filed on February 23,
`2010
`Harrison, B., et al., “Amplified Fluorescence Quenching in a
`Poly(p-phenylene)-Based Cationic Polyelectrolyte,” J. Am.
`Chem. Soc. 122: 8561-8562 (2000)
`Ego, C., et al., “Attaching Perylene Dyes to Polyfluorene: Three
`Simple, Efficient Methods for Facile Color Tuning of Light-
`Emitting Polymers,” J. Am. Chem. Soc. 125:437-443 (2003)
`Beljonne, D., et al., “Interchain vs. intrachain energy transfer in
`acceptor capped conjugated polymers,” PNAS 99: 10982-10987
`(2002)
`Claim Construction Order for the ’799 Patent, the ’673 Patent,
`and the ’113 Patent, The Regents of The University of California,
`and Becton, Dickinson and Company v. Affymetrix, Inc. and Life
`Technologies Corp., Civil Action No. 17-01394 (S.D. Cal., dated
`March 26, 2018)
`Burgess et al., “Through Bond Energy Transfer In Fluorescent
`Dyes For Labelling Biological Molecules,” U.S. Patent No.
`6,340,750 (filed December 14, 1999; issued January 22, 2002)
`
`
`
`- 4 -
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`
`Thermo
`Fisher
`Exhibit #
`
`Description
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`Reppy, et al., “Method For Detecting An Analyte By
`Fluorescence,” International Patent Application Publication No.
`WO 01/71317 (filed March 20, 2001; published September 27,
`2001)
`LeClerc, et al., “Detection of Negatively Charged Polymers
`Using Water-Soluble, Cationic, Polythiophene Derivatives,”
`International Publication No. WO 02/081735, (filed April 5,
`2002; published October 17, 2002)
`McQuade, D., et al., “Signal Amplification of a ‘Turn-On’
`Sensor:
`Harvesting the Light Captured by a Conjugated Polymer,” J. Am.
`Chem. Soc. 122: 12389-12390 (2000)
`Glazer, et al., “Dyes Designed For High Sensitivity Detection of
`Double-Stranded DNA,” U.S. Patent No. 5,783,687 (filed
`September 5, 1996; issued July 21, 1998)
`De Angelis, D., “Why FRET over genomics?”, Physiological
`Genomics 1: 93-99 (1999)
`Didenko, V., “DNA Probes Using Fluorescence Resonance
`Energy Transfer (FRET): Designs and Applications,”
`Biotechniques 31:1106-1121 (2001)
`LeClerc, M., “Optical and Electrochemical Transducers Based
`on Functionalized Conjugated Polymers,” Adv. Mater. 11: 1491-
`1498 (1999)
`Wang, J., et al., “Photoluminescence of Water-Soluble
`Conjugated Polymers: Origin of Enhanced Quenching by Charge
`Transfer,” Macromolecules 33: 5153-5158 (2000)
`Liu, B., et al., “Synthesis of a novel cationic water-soluble
`efficient blue photoluminescent conjugated polymer,” Chem.
`Comm. 551-552 (2000)
`Gaylord, B., et al., “DNA detection using water-soluble
`conjugated polymers and peptide nucleic acid probes,” PNAS 99:
`10954-10957 (2002)
`The Nobel Prize in Chemistry 2000, Conductive Polymers, The
`Royal Swedish Academy of Sciences
`
`
`
`- 5 -
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`
`Thermo
`Fisher
`Exhibit #
`
`Description
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`Chen, L., et al., “Highly sensitive biological and chemical
`sensors based on reversible fluorescence quenching in a
`conjugated polymer,” PNAS 96: 12287-12292 (1999)
`Liu, B., et al., “Shape-Adaptable Water-Soluble Conjugated
`Polymers,” J. Am. Chem. Soc. 125: 13306-13307 (2003)
`Curriculum Vitae of Dr. Kirk Schanze
`Swager, T.,, “Fluorescence Studies of Poly(p-
`phenyleneethyny1ene)s: The Effect of Anthracene Substitution,”
`J. Phys. Chem. 99: 4886-4893 (1995)
`Chen, et al., “Method For Detecting Biological Agents,” U.S.
`Patent Application Publication No. 2004/0023272 (filed April
`10, 2003; published February 5, 2004)
`Swager, T., “The Molecular Wire Approach to Sensory Signal
`Amplification,” Ace. Chem. Res. 31: 201-207 (1998)
`Huang, F., et al., “High-Efficiency, Environment-Friendly
`Electroluminescent Polymers with Stable High Work Function
`Metal as a Cathode: Green- and Yellow-Emitting Conjugated
`Polyfluorene Polyelectrolytes and Their Neutral Precursors,” J.
`Am. Chem. Soc. 126: 9845-9853 (2004)
`Ranger, M., et al., “New Well-Defined Poly(2,7-fluorene)
`Derivatives: Photoluminescence and Base Doping,”
`Macromolecules 30: 7686-7691 (1997)
`Bazan, “Methods and Compositions for Detection and Analysis
`of Polynucleotides Using Light Harvesting Multichromophores,”
`International PCT Application No. WO 2004/001379 (filed June
`20, 2003; published December 31, 2003)
`Pinto, M., et al., “Conjugated Polyelectrolytes: Synthesis and
`Applications,” Synthesis 9: 1293-1309 (2002)
`Wang, D., “Conjugated Polyelectrolyte as Novel Biosensors,”
`University of California Santa Barbara Doctoral Dissertation,
`September 2001
`Swager, et al., “Emissive Polymers And Devices Incorporating
`These Polymers,” International Patent Application Publication
`No. WO 99/57222 (filed May 5, 1999; published November 11,
`1999)
`
`
`
`- 6 -
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`
`Thermo
`Fisher
`Exhibit #
`
`Description
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`Hancock, et al., “Luminescent Polymer Particles,” U.S. Patent
`Application Publication No. 2003/0134959 (filed November 30,
`2001; published July 17, 2003)
`Complaint, The Regents of The University of California, and
`Becton, Dickinson and Company v. Affymetrix, Inc. and Life
`Technologies Corp., Case No. 17-01394 (S.D. Cal., dated July
`10, 2017)
`Plaintiff’s Opposition to Motion to Dismiss For Lack of
`Jurisdiction Pursuant to Rule 12(B)(1), The Regents of The
`University of California, and Becton, Dickinson and Company v.
`Affymetrix, Inc. and Life Technologies Corp., Case No. 17-01394
`(S.D. Cal., dated August 22, 2017)
`Tan, C., et al., “Photophysics, aggregation and amplified
`quenching of a water-soluble poly(phenylene ethynylene),”
`Chem. Comm. 446-447 (2002)
`Pschirer, N., et al., Fluorenone-Containing Poly(p-
`phenyleneethynylene)s (PPE) and Poly(fluorenyleneethynylene)s
`(PFE): Tuning the Solid-State Emission of Alkyne-Bridged
`Polymers by Interchain Energy Transfer,” Macromolecules 34:
`8590-8592 (2001)
`Andersson, M., et al., “Polythiophene with a free amino acid side
`chain,” Polymer Communications 32: 546-548 (1991)
`Wang, D., et al., “Biosensors from conjugated polyelectrolyte
`complexes,” PNAS 99: 49-53 (2002)
`LeClerc, “Optical Sensors Based on Hybrid Aptamer/Conjugated
`Polymer Complexes, ” U.S. Patent No. 8,409,797 (filed January
`10, 2007; issued April 2, 2013)
`Ewbank, P., et al., “Amine functionalized polythiophenes:
`synthesis and formation of chiral, ordered structures on DNA
`substrates,” Tetrahedron Letters 42 : 155-157 (2001)
`Nguyen, T., et al., “Control of Energy Transfer in Oriented
`Conjugated Polymer Mesoporous Silica Composites,” Science
`288: 652-656 (2000)
`Fan, C., et al., “Beyond superquenching: Hyper-efficient energy
`transfer from conjugated polymers to gold nanoparticles,” PNAS
`100: 6297-6301 (2003)
`
`
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`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`
`Thermo
`Fisher
`Exhibit #
`
`Description
`
`Supplemental Response of The Regents And Becton Dickinson
`To Interrogatory Nos. 5 and 6, The Regents of The University of
`California, and Becton, Dickinson and Company v. Affymetrix,
`Inc. and Life Technologies Corp., Case No. 17-01394 (S.D. Cal.,
`dated June 20, 2017)
`Perkel, J., “An Expanding Color Palette for Biotechnology,”
`Science, April 12, 2013 (BD00033050)
`Anderson, et al., “System for Rate Immunonephelometric
`Analysis,” U.S. Patent No. 4,157,871 (filed May 16, 1977; issued
`Jun. 12, 1979)
`Declaration of Kevin Burgess, Ph.D. in Support of Defendants’
`Claim Construction, The Regents of The University of California,
`and Becton, Dickinson and Company v. Affymetrix, Inc. and Life
`Technologies Corp., Case No. 17-01394 (S.D. Cal., dated
`January 25, 2018)
`Declaration of Timothy M. Swager, Ph.D. Regarding Claim
`Construction, The Regents of The University of California, and
`Becton, Dickinson and Company v. Affymetrix, Inc. and Life
`Technologies Corp., Case No. 17-01394 (S.D. Cal., dated
`January 26, 2018)
`Liu, B., et al., “Blue-Light-Emitting Cationic Water-Soluble
`Polyflourene Derivatives with Tunable Quaternization Degree,”
`Macromolecules 35: 4975-4982 (2002)
`Cardullo, et al., “Detection of nucleic acid hybridization by
`nonradiative fluorescence resonance energy transfer,” Proc. Nat.
`Acad. Sci. USA 85: 8790-8794 (1988)
`Ho, et al., “Colorimetric and Fluorometric Detection of Nucleic
`Acides Using Cationic Polythiophene Derivatives,” Angew.
`Chem. 114: 1618-1621 (2002)
`Burroughes, et al., “Light emitting diodes based on conjugated
`polymers,” Nature 347: 539-541 (1990)
`A Concise Dictionary of Chemistry, 2nd Ed., Oxford University
`Press, Oxford, UK (1990)
`Nelson, D., et al., Principles of Biochemistry, 4th Ed., W.H.
`Freeman and Company, New York (2005)
`
`1048
`
`1064
`
`1069
`
`1070
`
`1071
`
`1072
`
`1073
`
`1074
`
`1075
`
`1076
`
`1077
`
`
`
`- 8 -
`
`
`
`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`
`Description
`
`Alberts, B., et al., Molecular Biology of the Cell, Garland
`Publishing, Inc., New York (1983)
`Solvent Polarity Table, Miller’s Home, accessible at
`https://sites.google.com/site/miller00828/in/solvent-polarity-
`table (last accessed July 7, 2018)
`Bazan, et al., “Methods for Assaying a Sample for An
`Aggregant,” U.S. Patent No. 7,666,594 (filed Jan. 31, 2006;
`issued Feb. 23, 2010)
`Anderson, J., et al., “Nonspecific Flocculation of Diptheria
`Antitoxin, Toxin, and Toxoid, and Its Bearing on the Lf Titer,”
`Am. J. Public Health 23: 681-686 (1933)
`Matthews, R., Plant Virus Serology, Cambridge UP, Cambridge,
`UK, 1957
`Stork, M., et al., “Energy Transfer in Mixtures of Water-Soluble
`Oligomers: Effect of Charge, Aggregation, and Surfactant
`Complexation, Adv. Mater. 14: 361-366 (2002)
`
`Thermo
`Fisher
`Exhibit #
`
`1078
`
`1079
`
`1080
`
`1081
`
`1082
`
`1083
`
`
`
`IV. Person of ordinary skill in the art
`11. To determine the qualifications of a person of ordinary skill in the art
`
`to which the patent pertains, I have been asked to consider: (1) the educational
`
`level of the inventors; (2) the type of problems encountered in the art; (3) the
`
`prior art solutions to those problems; (4) the rapidity with which innovations are
`
`made; (5) the sophistication of the technology; and (6) the educational level of
`
`workers in the field. I have been informed that of the named inventors of the ’673
`
`patent, Guillermo Bazan was a Ph.D.-trained Professor and Bin Liu was a
`
`postdoctoral researcher in 2005. It is my understanding that a person of ordinary
`
`
`
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`
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`

`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`skill in the art (“POSA”) is a hypothetical person who is presumed to be aware of
`
`all pertinent art, thinks along conventional wisdom in the art, and is a person of
`
`ordinary creativity. A POSA in the technical field of the ’673 patent (conjugated
`
`polymeric aggregation sensors) would have had knowledge of the scientific
`
`literature concerning methods of synthesizing fluorescent conjugated polymers
`
`and using these polymers for detecting aggregants.
`
`12. Here, a POSA would typically have had (i) a Ph.D. in Chemistry, or in
`
`a related field in the chemical sciences, and have at least about two years of
`
`experience in chemical synthesis and application of fluorescent conjugated
`
`polymers; or (ii) a Master's degree in the same fields with at least about five years
`
`of the same experience. Also, a POSA may have worked as part of a
`
`multidisciplinary team and drawn upon not only his or her own skills, but of
`
`others on the team, e.g., to solve a given problem. For example, a biochemist,
`
`molecular biologist and a clinician specializing in detection of biological
`
`molecules may have been part of a team1.
`
`
`1 I understand that experts for both Thermo Fisher and Patent Owner have
`
`proposed a definition for a POSA in corresponding Federal court litigation
`
`regarding the '673 patent: The Regents of the University of California et al. v.
`
`Affymetrix, Inc. et al., Case No. 3:17-cv-01394 (CASD). I have reviewed the
`
`
`
`
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`

`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`State of the art before January 31, 2005
`13. Before January 31, 2005, the state of the art included the teachings
`
`V.
`
`provided by the references discussed in this Declaration. Additionally, a POSA,
`
`based on then-existing literature, would also have had general knowledge of the
`
`conjugated polymers and their use as biosensors.
`
`A. Conjugated polymers and their properties were well known by
`2005
`14. Conjugated polymers have a system of alternative single and double
`
`(or sometimes triple) bonds. TFS1024, 1-2; TFS1037, ¶¶[0112]-[0114]. As
`
`shown in the figure below, each bond of the conjugated polymer contains a
`
`sigma(σ)-bond between overlapping atomic s-orbitals of the atoms bonded
`
`together. TFS1024, 1-2; TFS1037, ¶¶[0112]-[0114]. An atomic orbital represents
`
`the possible locations of electrons in the molecule. Each double bond also
`
`
`definition of a POSA provided by Thermo Fisher's expert, Dr. Kevin Burgess
`
`(TFS1070, p. 6, ¶¶ 8 and 9), and Patent Owner's expert, Dr. Timothy Swager
`
`(TFS1071, pp. 3-4, ¶ 6). Both experts' definitions are not meaningfully different
`
`from my definition of a POSA above, and my opinions in this declaration would be
`
`the same under either experts' definition of a POSA.
`
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`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`contains a pi(π)-bond, which is made up over overlapping p-orbitals of the atoms
`
`bonded together. TFS1024, 1-2; TFS1037, ¶¶[0112]-[0114].
`
`
`
`15. The alternating double bonds with their overlapping p-orbitals give
`
`conjugated polymers a system of connected p-orbitals. An electron is able to
`
`move throughout this system of connected p-orbitals, covering a great distance
`
`along the conjugated polymer. TFS1024, 2; TFS1037, ¶¶[0112]-[0114]. As the
`
`electron is not limited to a specific bond location in the conjugated polymer and
`
`can move around the polymer, the conjugated polymer is considered to have a
`
`delocalized electronic structure. TFS1024, 2; TFS1037, ¶¶[0112]-[0114];
`
`TFS1023, 3:1:2.
`
`16. The delocalized electronic structure allows the conjugated polymers
`
`to absorb and emit energy. See, e.g., TFS1037, ¶¶[0113]-[0114]; TFS1024, 2;
`
`TFS1036, 9:30-10:15. Parts of the conjugated system may act as a chromophore,
`
`absorbing energy from light shone on the conjugated polymer and transmitting
`
`the absorbed energy through the conjugated polymer. TFS1036, 9:30-10:15;
`
`TFS1037, ¶¶[0109]-[0112]. As discussed below, in the context of the '673 patent,
`
`optically active units in the polymer act as signaling chromophores. This
`
`absorbed energy may be emitted or transferred to another chromophore through a
`
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`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`mechanism such as Förster resonance energy transfer (FRET) if the other
`
`chromophore is in close enough proximity. See, e.g., TFS1037, ¶¶[0113]-[0114];
`
`TFS1018, 4:1Figures 1B and 1C.
`
`17. Förster resonance energy transfer or fluorescence resonance energy
`
`transfer (FRET) occurs between two light-sensitive molecules (fluorophores or
`
`chromophores): a donor fluorophore and an acceptor fluorophore. The donor is
`
`excited by light radiation of a specific wavelength. Once excited, the donor then
`
`transfers energy to the acceptor via a dipole-dipole interaction. When the donor
`
`transfers its energy, the donor's fluorescence decreases, i.e., is quenched. Once
`
`the energy is transferred to the acceptor, it loses this energy either through a
`
`fluorescence emission of light or as heat (also known as non-radiative emission).
`
`TFS1019, 3:2:1.
`
`18. The donor and acceptor fluorophores each have absorption and
`
`emission spectra. The absorption spectrum is the range of wavelengths at which a
`
`chromophore absorbs radiation and the emission spectrum is the range of
`
`wavelengths at which a chromophore emits radiation when excited. See
`
`TFS1018, 4:1:1, 5:Figure 1A.
`
`19. In an energy transfer system such as FRET, the donor and acceptor
`
`have different absorption and emission spectra. For FRET to occur, the emission
`
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`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`spectrum of the donor must overlap with the absorption spectrum of the acceptor,
`
`as shown schematically in the figure below. See TFS1018, 4:1:1, 5 :Figure 1A.
`
`
`
`20. The overlap between the donor emission spectrum and the acceptor
`
`absorption spectrum allows emission from the donor to excite the acceptor. The
`
`acceptor then emits radiation in the wavelengths of the acceptor emission
`
`spectrum. TFS1018, 4:1; TFS1019, 3. Thus an excitation of the donor leads to
`
`energy transfer to the acceptor and a detected acceptor signal.
`
`21. Conjugated polymers were known to produce an "antenna effect" or
`
`"molecular wire effect" whereby the polymer collects light energy it is exposed to
`
`and transmits this energy along the length of the polymer to an acceptor. In this
`
`way, the conjugated polymer acts as an antenna or a wire for receiving and
`
`transmitting light energy much in the same way a radio antenna collects a radio
`
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`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`signal and transmits it to a speaker or the way a wire transmits electrical energy.
`
`For example, in discussing anthracene containing conjugated polymers, Swager
`
`notes that "[w]hen anthracene is incorporated into the backbones, the polymers
`
`act as antennae which harvest the optical energy and transfer it to the anthracene
`
`groups, resulting in emission from these chromophores." TFS1028, 8:1:1. Swager
`
`notes that this antenna effect has been demonstrated in a variety of polymeric
`
`systems. TFS1028, 12:1:4.
`
`22. Another paper by Swager's group also discusses how "molecular wires
`
`(conjugated polymers) can be used to amplify molecular chemosensors."
`
`TFS1030, 2-3, 8. And Harrison also notes that "[f]luoresence sensing is amplified
`
`by conjugated polymers because of the 'molecular wire effect'." TFS1009, 3:1:1.
`
`23. Thus a POSA would have known in January 2005 that conjugated
`
`polymers have the ability to harvest light energy and transfer it to a donor
`
`fluorophore. This excited energy state that is transferred is referred to as an
`
`exciton, which carries energy, but does not transfer charge. TFS1025, 3:1:2-
`
`3:2:1.
`
`B. Adaption of conjugated polymers for use in biosensing systems
`24. The initial uses of conjugated polymers was in providing light in
`
`electronic systems such as light emitting diodes (LEDs). TFS1075. But by the
`
`late 1990s, researches had realized that these conjugated polymers had use in
`
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`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`other applications, such as the detection of chemical and biological molecules.
`
`For example, LeClerc 1999 provides a short review of the applications of
`
`conjugated polymers in the late 1990s, and states that "conjugated polymers can
`
`now be rationally designed and optimized for the development of efficient
`
`display devices, sensors, diagnostic tools, etc." TFS1020, 3:2:1.
`
`25. Other researchers such as Liu 2000 noted the different potential uses
`
`of conjugated polymers. Liu stated that "[p]otential applications of water soluble
`
`conjugated polymers include the construction of active layers in organic light-
`
`emitting diodes through a layer-by-layer self-assembly approach, as buffer layer
`
`and emissive layer materials in inkjet printing fabricated organic LEDs, and as
`
`highly sensitive fluorescent sensory materials in living bodies." TFS1022,
`
`3:1:1 (emphasis added). And Inguanas noted that conjugated polymer-based
`
`biosensors "offer a key advantage compared to small molecules based
`
`biosensors" because of their sensitivity to "very minor perturbations, due to
`
`amplification by a collective system response." TFS1006, 1:17-19.
`
`26. The advantageous properties of conjugated polymers led researchers
`
`to adapt conjugated polymers for use in analyte detection systems. Wang
`
`summarizes the thinking in the field at the time:
`
`conjugated
`the optoelectronic properties of
`Research on
`(semiconducting) polymers has created opportunities for a number of
`applications,
`such
`as
`light-emitting
`diodes,
`light-emitting
`
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`Inter Partes Review of U.S. Patent No. 8,110,673
`Declaration of Kirk S. Schanze, Ph.D. (Exhibit 1002)
`cells,
`solid-state
`lasers,
`solar
`cells,
`and
`electrochemical
`photodetectors. The recent discovery of more than a millionfold
`amplification of the sensitivity to fluorescence quenching by Chen et
`al. opens an opportunity for conjugated polymers in biological
`and chemical sensors for use
`in medical diagnostics and
`toxicology.
`
`TFS1021, 4:1:1 (emphasis added).
`
`27. Multiple groups had begun to see the potential of conjugated polymers
`
`in biosensing systems by the early 2000s. A dissertation by Wang from 2001
`
`states that "besides the tremendous research and industrial progresses in using
`
`conjugated polymers as … LEDs …, conjugated polymers were found