`
`
`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 IPR2018-01347
`Patent No. 9,085,799
`_____________________
`
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 9,085,799
`
`
`
`
`
`
`
`
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`

`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`TABLE OF CONTENTS
`
`2. 
`
`
`Overview ......................................................................................................... 1 
`I. 
`Standing (37 C.F.R. § 42.104(a)) ................................................................... 2 
`II. 
`Statement of the precise relief requested and the reasons therefore .............. 2 
`III. 
`IV.  Overview ......................................................................................................... 3 
`A. 
`The '799 patent disclosure and claims ................................................... 3 
`B. 
`Person of ordinary skill in the art ("POSA") ......................................... 7 
`C. 
`State of the art ........................................................................................ 8 
`Identification of the challenge (37 C.F.R. § 42.104(b)) ............................... 13 
`V. 
`VI.  Claim construction ........................................................................................ 14 
`A. 
`"Greater than 4 fold increase in fluorescence emission … in the
`absence of the polymer" ...................................................................... 15 
`1. 
`"In the absence of the polymer" requires that the polymer is
`not physically present in order for the comparison to be made 16 
`"Greater than 4 fold" is an open ended limitation ................... 18 
`2. 
`VII.  Claims 1, 3, 4, 6 and 7 are not entitled to priority before September 12,
`2007 .............................................................................................................. 21 
`A. 
`The inventors did not possess the claimed method when they filed
`their earlier, narrower, First and Provisional Applications ................. 24 
`The First and Provisional Applications do not describe the full
`scope of the broadly claimed "greater than 4 fold increase in
`fluorescence emission … in the absence of the polymer" .................. 25 
`1. 
`The First Application discloses only an "~4 fold" increase in
`emission ................................................................................... 26 
`The Provisional Application also discloses only an "~4 fold"
`increase in emission in the absence of the polymer ................. 29 
`The limited disclosure in the First and Provisional Applications is
`insufficient to provide written description of the full scope of
`"greater than 4 fold increase in emission … in the absence of the
`polymer" .............................................................................................. 30 
`
`B. 
`
`C. 
`
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`

`

`1. 
`
`2. 
`
`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`The First and Provisional Applications do not disclose a
`representative number of species ............................................. 31 
`The First and Provisional Applications do not provide a
`structure-function correlation sufficient to describe the full
`scope of the claimed greater than 4 fold increase in
`fluorescence emission .............................................................. 32 
`VIII.  Bazan teaches an embodiment that has each and every element of the
`challenged claims, arranged as claimed ....................................................... 37 
`A. 
`Bazan anticipates claim 1 .................................................................... 40 
`B. 
`Bazan anticipates claim 3 .................................................................... 48 
`C. 
`Bazan anticipates claim 4 .................................................................... 49 
`D. 
`Bazan anticipate claims 6 and 7 .......................................................... 50 
`IX.  Patent Owner has waived any right to Sovereign Immunity ........................ 52 
`X.  Mandatory Notices (37 C.F.R. § 42.8(a)(1)) ................................................ 53 
`
`
`
`
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`- ii -
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`

`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`EXHIBIT LIST
`
`Thermo Fisher
`Scientific Exhibit #
`
`Description
`
`1001
`
`1002
`1003
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`Bazan, "Methods and Compositions For Detection and
`Analysis of Polynucleotides Using Light Harvesting
`Multichromophores," U.S. Patent No. 9,085,799 (filed
`August 14, 2014; issued July 21, 2015)
`Declaration of Kirk S. Schanze, Ph.D.
`Provisional application 60/406,266, filed August 26, 2002
`File History of U.S. Application No. 10/648,945, filed
`August 26, 2003
`Bazan, "Methods and Compositions For Detection and
`Analysis of Polynucleotides Using Light Harvesting
`Multichromophores," U.S. Patent No. 7,270,956 (filed
`August 26, 2003; issued September 18, 2007)
`File History of U.S. Application No. 11/854,365, filed
`September 12, 2007
`Bazan, "Compositions For Detection and Analysis of
`Polynucleotides Using Light Harvesting
`Multichromophores," U.S. Patent No. 7,629,448 (filed
`September 12, 2007; issued December 18, 2009)
`File History of U.S. Application No. 12/632,734, filed
`December 7, 2009
`Bazan, "Methods and Compositions For Detection and
`Analysis of Polynucleotides Using Light Harvesting
`Multichromophores." U.S. Patent No. 8,227,187 (filed
`December 7, 2009; issued July 24, 2012)
`File History of U.S. Application No. 13/544,303, filed July
`9, 2012
`Bazan, "Methods and Compositions For Detection and
`Analysis of Polynucleotides Using Light Harvesting
`Multichromophores," U.S. Patent No. 8,617,814 (filed July
`9, 2012; issued December 31, 2013)
`File History of U.S. Application No. 14/086,532, filed
`November 21, 2013
`
`
`
`- iii -
`
`

`

`Thermo Fisher
`Scientific Exhibit #
`
`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`
`Description
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`Bazan, "Methods and Compositions For Detection and
`Analysis of Polynucleotides Using Light Harvesting
`Multichromophores," U.S. Patent No. 8,841,072 (filed
`November 21, 2013; issued September 23, 2014)
`File History of U.S. Application No. 14/460,245, filed
`August 14, 2014
`Kool, "Fluorescent Nucleoside Analogs and Combinatorial
`Fluorophore Arrays Comprising Same," International
`Publication No. WO 01/044220 (filed December 13, 2000;
`published June 21, 2001)
`Kang, T., et al., "Photoluminescence properties of various
`polythiophene derivatives," Synthetic Metals 69: 377-378
`(1995)
`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)
`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)
`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
`
`
`
`- iv -
`
`

`

`Thermo Fisher
`Scientific Exhibit #
`
`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`
`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)
`Bazan, "Methods and Compositions For Detection and
`Analysis of Polynucleotides Using Light Harvesting
`Multichromophores," U.S. Patent Application Publication
`No. 2004/0142344, (filed August 26, 2003; published July
`22, 2004)
`Curriculum Vitae for Kirk S. Schanze, Ph.D.
`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)
`Gruber, H., et al., "Biotin-Fluorophore Conjugates with
`Poly(ethylene glycol) Spacers Retain Intense Fluorescence
`after Binding to Avidin and Streptavidin," Bioconjugate
`Chem. 8: 552-559 (1997)
`Haugland, R., Handbook of Fluorescent Probes and
`Research Products, 9th Ed., Molecular Probes, Inc. (2002)
`Haugland, R., Handbook of Fluorescent Probes and
`Research Products, 8th Ed., Molecular Probes, Inc. (2001)
`Pinto, M. and Schanze, K., "Conjugated Polyelectrolytes:
`Synthesis and Applications," Synthesis 9: 1293 - 1309 (2002)
`Alberts, Molecular Biology of the Cell, 2nd ed., Garland
`Publishing, Inc. (1989)
`Swager et al., "Emissive Polymers and Devices
`Incorporating These Polymers," International Publication
`No. WO 99/57222 (filed May 5, 1999; published November
`11, 1999)
`
`
`
`- v -
`
`

`

`Thermo Fisher
`Scientific Exhibit #
`
`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`
`Description
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`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 et al.
`v. Affymetrix, Inc. et al., Case No. 17-01394 (S.D. Cal., dated
`July 10, 2017)
`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)
`Harrison, B., et al., "Amplified Fluorescence Quenching in a
`Poly(p-phenylene)-Based Cationic Polyelectrolyte," J. Am.
`Chem. Soc. 122: 8561-8562 (2000)
`Reppy et al., "Method For Detecting An Analyte By
`Fluorescence," International 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)
`Cardullo, R., et al., "Detection of nucleic acid hybridization
`by nonradiative fluorescence resonance energy transfer"
`PNAS 85: 8790-8794 (1988)
`Claim Construction Order For the '799 Patent, the '673
`Patent, and the '113 Patent, The Regents of the University of
`California et al. v. Affymetrix, Inc. et al., Civil Action No.
`17-01394 (S.D. Cal., dated March 26, 2018)
`Deposition Transcript for Timothy M. Swager, Ph.D., The
`Regents of the University of California et al. v. Affymetrix,
`Inc. et al., Case No. 17-01394 (S.D. Cal., dated September
`16, 2017)
`Plaintiff's Claim Construction Brief, The Regents of the
`University of California et al. v. Affymetrix, Inc. et al., Case
`No. 17-01394 (S.D. Cal., dated February 23, 2018)
`
`
`
`- vi -
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`

`

`Thermo Fisher
`Scientific Exhibit #
`
`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`
`Description
`
`1047
`
`1048
`
`1049
`
`1050
`
`1051
`
`1052
`
`Bazan, "Methods and Compositions For Detection and
`Analysis Of Polynucleotides Using Light Harvesting
`Multichromophores," U.S. Patent No. RE46,817 (filed
`March 29, 2017; issued May 1, 2018)
`File History of U.S. Application No. 15/473,316, filed on
`March 29, 2017
`Declaration of Kevin Burgess, Ph.D. In Support of
`Defendants' Claim Construction, The Regents of the
`University of California et al. v. Affymetrix, Inc. et al., Civil
`Action No. 17-01394 (S.D. Cal., dated January 26, 2018)
`Declaration of Timothy M. Swager, Ph.D. Regarding Claim
`Construction, The Regents of the University of California et
`al. v. Affymetrix, Inc. et al., Civil Action No. 17-01394 (S.D.
`Cal., dated January 26, 2018)
`File History for U.S. Appl. No. 15/934,874, filed on March
`23, 2018
`Plaintiffs' Opposition to Motion To Dismiss For Lack of
`Jurisdiction Pursuant to Rule 12(B)(1), The Regents of the
`University of California et al. v. Affymetrix, Inc. et al., Civil
`Action No. 17-01394 (S.D. Cal., dated August 22, 2017)
`
`
`
`- vii -
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`

`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`Thermo Fisher Scientific Inc., Life Technologies Corp., and Affymetrix, Inc.
`
`petition for Inter Partes Review, seeking cancellation of claims 1, 3, 4, 6, and 7 of
`
`U.S. Patent No. 9,085,799 (TFS1001) as unpatentable under 35 U.S.C. § 102(b).
`
`This petition demonstrates that a reasonable likelihood exists that Petitioner will
`
`prevail in proving that each of claims 1, 3, 4, 6, and 7 of the '799 patent are
`
`unpatentable as anticipated.
`
`I.
`
`Overview
`
`The '799 patent is the sixth patent to issue in a chain of continuations sharing
`
`identical specifications and differing only in their claims.
`
`The challenged claims are directed to a method of using a light harvesting
`
`multichromophore that comprises (a) a signaling chromophore and (b) a "water-
`
`soluble conjugated polymer." The claims also require that the conjugated polymer
`
`"transfers energy from its excited state to the signaling chromophore to provide a
`
`greater than 4 fold increase in fluorescence emission from the signaling
`
`chromophore than can be achieved by direct excitation of the signaling
`
`chromophore in the absence of the polymer." But this Petition will show that the
`
`earlier applications in the priority chain do not describe sufficient species or a
`
`structure-function correlation to show that Patent Owner possessed the full scope
`
`of its now claimed "greater than 4 fold increase" when it filed its earlier
`
`applications. Instead, the priority applications disclose only a single species within
`
`
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`- 1 -
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`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`that range of an "~4 fold" increase in emission. This single disclosure that straddles
`
`the very lower end of the open-range now claimed does not support the '799
`
`patent's claim of priority benefit to the earlier applications. Nor do the priority
`
`applications provide the skilled artisan with sufficient detail about the structure of
`
`the claimed water-soluble conjugated polymers to support the full range of
`
`fluorescence emission increases "greater than 4 fold" required by every challenged
`
`claim. This lacking description means that the challenged claims are not entitled to
`
`claim priority benefit to their earlier-filed applications.
`
`Since the challenged claims are not entitled to claim priority to their earlier-
`
`filed priority applications, the first published application in the family ("Bazan";
`
`TFS1026) is prior art to, and anticipates, the challenged claims. Accordingly, IPR
`
`should be instituted as a reasonable likelihood exists that Petitioner will prevail in
`
`proving that each of claims 1, 3, 4, 6, and 7 of the '799 patent are unpatentable.
`
`II.
`
`Standing (37 C.F.R. § 42.104(a))
`
`Petitioners certify that the '799 patent is available for IPR and Petitioners are
`
`not barred or estopped from requesting IPR of any of the challenged claims.
`
`III. Statement of the precise relief requested and the reasons therefore
`
`The Office should institute IPR under 35 U.S.C. §§ 311-319, and 37 C.F.R.
`
`§§ 42.1-.80 and 42.100-42.123, and cancel claims 1, 3, 4, 6, and 7 of the '799
`
`patent as unpatentable under pre-AIA 35 U.S.C. § 102(b) for the reasons explained
`
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`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`below. This petition is accompanied and supported by the declaration of Dr.
`
`Schanze (TFS1002) an expert in developing optical sensors containing fluorescent
`
`conjugated polymers and signaling chromophores, and using these sensors for
`
`detecting binding events. Petitioner's detailed, full statement of the reasons for
`
`relief requested is provided in §§ VII-VIII.
`
`IV. Overview
`A. The '799 patent disclosure and claims
`
`The '799 patent, entitled "Methods and Compositions for Detection and
`
`Analysis of Polynucleotides Using Light Harvesting Multichromophores," issued
`
`on July 21, 2015, from U.S. Appl. No. 14/460/245 (TFS1014), which was filed on
`
`August 14, 2014. TFS1001, face page. The '799 patent is a continuation of and
`
`claims priority to the following U.S. Appl. Nos.: 14/086,532 (TFS1012), filed
`
`November 21, 2013, now USPN 8,841,072 (TFS1013) (reissued as USPN
`
`RE46,817 (TFS1047) on May 1, 2018 from 15/473,316 (TFS1048), filed March
`
`29, 2017), which is a continuation of 13/544,303 (TFS1010), filed July 9, 2012,
`
`now USPN 8,617,814 (TFS1011), which is a continuation of 12/632,734
`
`(TFS1008), filed December 7, 2009, now 8,227,187 (TFS1009), which is a
`
`continuation of 11/854,365 (TFS1006), filed September 12, 2007, now 7,629,448
`
`(TFS1007), which is a division of 10/648,945 (TFS1004), filed August 26, 2003,
`
`now 7,270,956 (TFS1005), which claims priority benefit to Provisional
`
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`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`Application No. 60/406,266, filed August 26, 2002 (TFS1003). Id. The graphic
`
`below is the tree for the '799 patent family:
`
`The detection method of the '799 patent has "at least two components; (a) a
`
`
`
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`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`cationic multichromophore, and (b) a 'sensor polynucleotide' (Oligo-C*)
`
`comprising an anionic polynucleotide conjugated to a signaling chromophore."
`
`TFS1001, 4:14-17; see also 10:53-12:45 ("The Polycationic Multichromophore");
`
`12:46-57 ("The Sensor Polynucleotide"); and 12:58-14:58 ("The Signaling
`
`Chromophore"). Together, these components are used to detect target
`
`polynucleotides in a sample. Id., 8:20-67 ("The Sample"). The graphic below
`
`illustrates the claimed multichromophore (A); and its application in a detection
`
`method (B), as a POSA would have understood it:
`
`TFS1002, ¶¶73-77.
`
`As the graphic illustrates, the signaling chromophore (labeled C*) can be
`
`
`
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`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`attached to a sensor polynucleotide. TFS1001, 12:46-57; 12:58-14:58. The sensor
`
`polynucleotide "is anionic," has a "predetermined sequence," and "is
`
`complementary to the target polynucleotide to be assayed." Id. at 12:47-49.
`
`According to the '799 patent, the "multichromophores used in the present invention
`
`are polycationic and can interact with a sensor polynucleotide electrostatically." Id.
`
`at 11:41-43.
`
`
`
`When a target polynucleotide is present in a sample, the sensor
`
`polynucleotide hybridizes to the target polynucleotide, "resulting in an increase in
`
`negative charge density along the DNA strand." Id., 3:54-56. Electrostatic
`
`interactions between the thus-formed negatively-charged duplex DNA and the
`
`positively-charged conjugated polymer bring the conjugated polymer into a close
`
`proximity to the signaling chromophore (C*). Id., 3:47-63. This close proximity
`
`results in energy transfer (labeled "FRET" in (B), which stands for "Forster
`
`Resonance Energy Transfer") from the conjugated polymer to the signaling
`
`chromophore (C*). Id. Emission of light from the excited chromophore indicates
`
`the presence of the target polynucleotide in the sample. Id., 4:6-11.
`
`The '799 patent claims. The '799 patent has eight claims. Claim 1 is the
`
`only independent claim, and recites:
`
`1. A method comprising:
`
`
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`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`(a) contacting a sample with a light harvesting
`multichromophore system, the system comprising:
`
`i) a signaling chromophore; and
`
`ii) a water-soluble conjugated polymer comprising a
`delocalized electronic structure, wherein the polymer can
`transfer energy from its excited state to the signaling
`chromophore to provide a greater than 4 fold increase in
`fluorescence emission from the signaling chromophore than
`can be achieved by direct excitation of the signaling
`chromophore in the absence of the polymer;
`
`(b) applying a light source to the sample; and
`
`(c) detecting whether light is emitted from the signaling
`chromophore.
`
`TFS1001, 21:51-65.
`
`B. Person of ordinary skill in the art ("POSA")
`
`A 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 '817 patent (conjugated
`
`polymer energy transfer detection systems) would have had knowledge of the
`
`scientific literature concerning methods of synthesizing fluorescent conjugated
`
`polymers and signaling chromophores, and using these polymers and
`
`chromophores for detecting binding events. TFS1002, ¶11.
`
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`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`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 team. Id., ¶12.
`
`In the concurrent litigation captioned The Regents of the University of
`
`California et al. v. Affymetrix, Inc. et al., Case No. 3:17-cv-01394 (CASD), experts
`
`for both Thermo Fisher and Patent Owner have proposed a definition for a POSA.
`
`TFS1049, ¶¶8 and 9; TFS1050, ¶6. Dr. Schanze confirmed that both experts'
`
`definitions are not meaningfully different from the definition of a POSA above.
`
`TFS1002, FN1. Dr. Schanze also confirmed that his analysis and conclusions
`
`would be unchanged if he had instead applied the POSA definition used by the
`
`litigation experts. Id.
`
`C. State of the art
`
`By August 2002 researchers were regularly using sensing systems based on
`
`the theory of Forster resonance energy transfer (also called fluorescence resonance
`
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`

`

`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`energy transfer; "FRET") for the detection of analytes. TFS1019, 3; TFS1002,
`
`¶13. FRET involves energy transfer between two chromophores: a donor
`
`chromophore and an acceptor chromophore.
`
`In a FRET-based system, a donor chromophore is excited by light radiation
`
`at a certain wavelength. When an acceptor chromophore is in close proximity to
`
`the donor, the excited donor transfers energy to the acceptor through a dipole-
`
`dipole interaction. The excited acceptor then dissipates this excess energy either
`
`by a fluorescence emission of light or as heat. TFS1019, 3; TFS1002, ¶14. The
`
`figure below, which was prepared by Dr. Schanze, illustrates a POSA's
`
`understanding of a typical FRET-based system:
`
`Donor
`
`Acceptor
`
`
`
`In a FRET system, the donor chromophore and acceptor chromophore each
`
`have different spectra wavelengths at which each chromophore absorbs and emits
`
`radiation. TFS1002, ¶15. For FRET to occur, the emission spectrum of the donor
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`must overlap with the absorption spectrum of the acceptor, as shown
`
`schematically below. When there is overlap, excitation within the donor
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`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`absorption spectrum causes a signal in the acceptor emission spectrum. TFS1018,
`
`4:1; TFS1019, 3; TFS1002, ¶16.
`
`
`
`TFS1002, ¶16. Thus, as Dr. Schanze confirms, a POSA in August 2002 would
`
`have known that a FRET-based system has only two basic requirements: (i) the
`
`donor and the acceptor are in close enough proximity to each other for energy
`
`transfer, and (ii) the donor emission spectrum overlaps with the acceptor
`
`absorption spectrum. TFS1002, ¶¶13-18.
`
`The field had described a variety of small-molecule fluorescent dyes, many
`
`of which were commercially available, for use in various FRET systems by
`
`August 2002. TFS1020, 9:36-45; TFS1043, Abstract; TFS1039, 3:2:1; TFS1041,
`
`Tables 1 and 2; TFS1015, 55: Example 8; TFS1016, Abstract; TFS1017, Table 1;
`
`TFS1002, ¶19. As Dr. Schanze explains, selection of donor and acceptor dyes was
`
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`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`routine well before 2002—all that was needed was an overlap between the
`
`acceptor emission spectrum and the donor absorption spectrum, and a
`
`physicochemical compatibility of the two (e.g., aqueous solubility). TFS1018,
`
`4:1:1; TFS1019, 3:2:1; TFS1002, ¶16-22. As a rule of thumb, in matching a donor
`
`to an acceptor, researchers looked to maximize overlap in emission/absorption
`
`spectra for best FRET signal. TFS1018, 4:1:1; TFS1019, 3:2:1; TFS1002, ¶¶16-
`
`22,123.
`
`In addition to small molecule dyes, fluorescent conjugated polymers were
`
`becoming increasingly popular as donors in FRET systems by August 2002.
`
`TFS1002, ¶27; see also, TFS1039, 3:1:1; TFS1042, 4:24-29; TFS1021, 4:1:1;
`
`TFS1040, 3:1:1; TFS1022, 3:1:1; and TFS1028, 8:1:1. Conjugated polymers are
`
`polymeric molecules composed of multiple monomeric subunits having
`
`alternating single and multiple bonds (i.e., double or triple bonds) that form a
`
`system of connected atomic orbitals. TFS1002, ¶27. As Dr. Schanze explains, this
`
`arrangement allow electrons to be delocalized over the length of the polymers.
`
`TFS1002, ¶¶28-29. Because of the delocalized electronic structure and the
`
`presence of multiple chromophoric monomers, conjugated polymers are able to
`
`harvest light energy and transmit it along the length of the polymer. See, e.g.,
`
`TFS1028, 8:1:1; TFS1040, 3:1:1; TFS1024, 1-2; TFS1030, 2:2:2-3:1:2; TFS1002,
`
`¶¶27-29. This energy transfer along the polymeric chain was known in the art as
`
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`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`the "antenna effect" or "molecular wire effect." TFS1002, ¶¶30-33. If there is
`
`another chromophore in energy transferring proximity to an excited conjugated
`
`polymer, the polymer can transfer the energy to the chromophore, e.g., via FRET.
`
`Id.
`
`By August 2002, researchers had demonstrated that this "molecular wire
`
`effect" results in an amplified energy transfer between a conjugated polymer and
`
`another chromophore. TFS1040, 3:1:1; TFS1030, 2:2:1; TFS1028, 8:1:1;
`
`TFS1002, ¶56. What is more, it was known that when a conjugated polymer
`
`transfers energy to another chromophore, that chromophore's emission is
`
`increased compared to direct excitation of the chromophore. TFS1030, 2:2:2-
`
`3:1:2; TFS1002, ¶56. Indeed, the field had demonstrated the antenna effect in
`
`FRET systems prior to August 2002. For example, McQuade demonstrated a
`
`significant increase in acceptor fluorescence obtained by excitation of a
`
`conjugated polymer donor compared the fluorescence of the directly excited
`
`acceptor in the presence of the polymer. TFS1039, 4:1:3; TFS1002, ¶¶59-60.
`
`Harrison also demonstrated a significant increase in acceptor fluorescence
`
`following excitation of a conjugated polymer donor. TFS1040, 3:1:1; TFS1002,
`
`¶¶61-63.
`
`As the signal obtained from FRET is highly dependent on the distance
`
`between the donor and acceptor, researchers recognized the usefulness of FRET in
`
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`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`detecting the binding of biological molecules in the 1970s and began using FRET
`
`for studying protein-protein interactions. TFS1019, 3; TFS1002, ¶18. Developing
`
`on the protein-protein systems, researchers began to use FRET to measure nucleic
`
`acid binding (i.e., hybridization) in the mid-1980s. TFS1019, 5-15; TFS1002, ¶18.
`
`By August 2002, biosensing FRET systems had been developed for
`
`detection of various biological molecules, including nucleic acids. TFS1002, ¶¶18,
`
`47-55; see also, TFS1015, 3:2; TFS1041, 2:7-10; TFS1043, Abstract; TFS1042,
`
`3:6-10; TFS1020, 1:20-23. These biosensing FRET systems comprised energy
`
`transfer from dye to dye (TFS1043, 2:2:2, Figure 1; TFS1020, Figure 1, 8:39-
`
`9:47; TFS1015, 4, Example 8 ), from conjugated polymer to dye (TFS1041,
`
`Example 2; TFS1015, Example 10) or from conjugated polymer to quencher
`
`(TFS1025, Abstract, Figure 2; TFS1029, Examples 1, 4 and 5).
`
`V.
`
`Identification of the challenge (37 C.F.R. § 42.104(b))
`
`Petitioners requests inter partes review of claims 1, 3, 4, 6, and 7 of the '799
`
`patent as anticipated by US2004/0142344 ("Bazan"; TFS1026). Per 37 C.F.R.
`
`§ 42.6(c), copies of the cited references accompany the Petition. Bazan published
`
`on July 22, 2004. Because the '799 patent is not entitled to claim priority benefit to
`
`its August 26, 2003 and August 26, 2002 priority filing dates, Bazan qualifies as
`
`prior art under §102(b) to the '799 patent's next possible priority date, September
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`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`
`12, 2007.1
`
`VI. Claim construction
`
`In the concurrent litigation, the court construed the terms "sample,"
`
`"multichromophore system," "polymer," and "water soluble conjugate polymer" as
`
`shown below. TFS1044, 6-21. Petitioner adopts those claim constructions for the
`
`purposes of this proceeding in line with the proposed modification to rules
`
`41.100(b), 42.200(b), and 42,300(b), requiring that the Board apply a Phillips-type
`
`claim construction analysis in post-grant proceedings to provide consistency with
`
`district court litigation. See 83 FR 21221-21226.
`
`Claim term
`
`Construction
`
`"sample" TFS1001, 21:63
`
`"a biological material that is analyzed for a
`target polynucleotide" TFS1044, 7-12.
`
`"multichromophore system"
`TFS1001, 21:52-53.
`
`"a polycationic multichromophore" TFS1044,
`12-15.
`
`"water soluble conjugated
`
`"a conjugated polymer that is water soluble at
`
`
`1Petitioner does not concede that the '799 patent is entitled to any of its
`
`possible priority dates: September 12, 2007; December 7, 2009; July 9, 2012; or
`
`November 21, 2013.
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`polymer" TFS1001, 21:55.
`
`"polymer"
`
`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`the time the sample is contacted with the light-
`harvesting multichromophore system in the
`performance of the method" TFS1044, 15-16.
`
`"a molecule with two or more monomeric
`repeat units" TFS1044, 19-21.
`
`
`The court also construed the claim element requiring that "the polymer can
`
`transfer energy from its excited state to the signaling chromophore to provide a
`
`greater than 4 fold increase in fluorescence emission from the signaling
`
`chromophore than can be achieved by direct excitation of the signaling
`
`chromophore in the absence of the polymer." TFS1001, 21:56-62; TFS1044, 16-
`
`19. Because that construction is particularly pertinent to this petition, it is
`
`discussed in more detail below.
`
`Any terms in the '799 patent claims not specifically construed in the
`
`concurrent litigation are to be given their plain and ordinary meaning as
`
`understood by a POSA.
`
`A. "Greater than 4 fold increase in fluorescence emission … in the
`absence of the polymer"
`
`Every challenged claim requires that the "polymer can transfer energy from
`
`its excited state to the signaling chromophore to provide a greater than 4 fold
`
`increase in fluorescence emission from the signaling chromophore than can be
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`Petition for Inter Partes
`Review of U.S. Patent No. 9,085,799
`achieved by direct excitation of the signaling chromophore in the absence of the
`
`polymer." TFS1001, 21:56-62. The district court construed this claim element to
`
`mean: "the polymer