Trials@uspto.gov
`571-272-7822
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` Paper No. 11
` Entered: February 7, 2019
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
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`THERMO FISHER SCIENTIFIC, INC.,
`Petitioner,
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`v.
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`THE REGENTS OF THE UNIVERSITY OF CALIFORNIA,
`Patent Owner.
`____________
`
`
`
`Case IPR2018-01370
`Patent 8,110,673 B2
`____________
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`Before ERICA A. FRANKLIN, MICHELLE N. ANKENBRAND, and
`JOHN E. SCHNEIDER, Administrative Patent Judges.
`
`ANKENBRAND, Administrative Patent Judge.
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`DECISION
`Denying Institution of Inter Partes Review
`35 U.S.C. § 314(a)
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`IPR2018-01370
`Patent 8,110,673 B2
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`I.
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`INTRODUCTION
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`Thermo Fisher Scientific, Inc. (“Petitioner”) filed a Petition requesting
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`an inter partes review of claims 1–3, 6–12, 14–17, and 19 of U.S. Patent No.
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`8,110,673 B2 (Ex. 1001, “the ’673 patent”). Paper 1 (“Pet.”). The Regents
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`of the University of California (“Patent Owner”) filed a Preliminary
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`Response to the Petition. Paper 8 (“Prelim. Resp.”).
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`We have authority under 35 U.S.C. § 314 to determine whether to
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`institute an inter partes review. Upon considering the Petition and the
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`Preliminary Response, along with the circumstances involved in this case,
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`we determine that Petitioner does not show a reasonable likelihood that it
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`would prevail in showing the unpatentability of at least one challenged
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`claim. Accordingly, we deny the Petition and decline to institute an inter
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`partes review.
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`II.
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`BACKGROUND
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` Related Matters
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`Petitioner and Patent Owner identify an ongoing district court
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`proceeding involving the ’673 patent: The Regents of the University of
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`California et al. v. Affymetrix, Inc. et al., No. 3:17-cv-01394 (CASD).
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`Pet. 69; Paper 4, 2. The parties also note that Petitioner concurrently filed a
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`separate petition involving the ’673 patent (IPR2018-01370) and, shortly
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`before, filed two petitions involving a related patent, U.S. Patent No.
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`8,835,113 B2 (IPR2018-01367 and IPR2018-01368). Pet. 69–70; Paper 4,
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`1–2.
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` The ’673 Patent
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`The ’673 patent, titled “Aggregation Sensor and Solutions and Kits
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`Comprising the Same,” issued on February 7, 2012. Ex. 1001, [45], [54].
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`2
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`The ’673 patent relates to an aggregation sensor for detecting and analyzing
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`aggregants in a sample. Id. at 1:26–27. According to the specification,
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`“[t]here is a continuing need in the art for methods of detecting and
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`analyzing particular biomolecules [i.e., aggregants] in a sample, and for
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`compositions and articles of manufacture useful in such methods.” Id. at
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`1:56–59. An aggregant or biomolecule to be assayed may include, for
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`example, a polysaccharide, a polynucleotide, a peptide, or a protein. Id. at
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`15:56–58. “The aggregation sensor comprises a component that can bind to
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`an aggregant or class of aggregants.” Id. at 10:10–12.
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`The specification further explains that “[c]onjugated polymers have
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`proven useful as light gathering molecules in a variety of settings.” Id. at
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`1:49–50. In particular, “[w]ater-soluble conjugated polymers such as
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`cationic conjugated polymers (CCPs) have been used in bioassays to
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`improve detection sensitivity and provide new routes of selectivity in
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`analyzing biomolecules.” Id. at 1:51–55. The molecular structure of those
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`molecules are of interest in DNA and RNA detection methods because it
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`“allows for a collective response and, therefore, optical amplification of
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`fluorescent signals.” Id. at 2:32–37. Specifically, “[t]he large number of
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`optically active units along the polymer chain increases the probability of
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`light absorption, relative to small molecule counterparts.” Id. at 2:37–39.
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`The presence of target DNA in a sample may be detected upon delivery of
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`excitations to fluorophores, using facile fluorescence resonance energy
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`transfer (FRET). Id. at 2:39–42.
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`The specification explains that “[r]ecent studies indicate that energy
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`transfer between segments in conjugated polymers may be substantially
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`more important than along the backbone” and that external perturbations that
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`decrease the elongation of the backbone, or that bring its segments closer
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`together, may be used to modify emissive properties of the polymer in
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`solution. Id. at 2:43–49. Based on that information, the specification states
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`that the inventors recognized “a small number of fluorescent units within a
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`polymer sequence could be activated by structural changes that compressed
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`or aggregated the polymer chains to ultimately change the emission color,”
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`and then designed a cationic conjugated polymer structure in accordance
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`with that principle. Id. at 2:50–55. According to the specification,
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`“[e]lectrostatic complexation with negatively charged DNA can be used to
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`reduce the average intersegment distance. When combined with a
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`fluorophore labeled peptide nucleic acid (PNA) strand, the polymer can be
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`used to design a three color DNA detection assay.” Id. at 2:55–60.
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`Of the challenged claims, claim 1 is independent and illustrative of the
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` Illustrative Claim
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`claimed subject matter. Claim 1 recites:
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`1. An aggregation sensor soluble in a polar medium
`comprising:
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`(a) a conjugated polymer comprising
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`a plurality of first optically active units forming a
`conjugated system, having a first absorption wavelength at
`which the first optically active units absorbs light to form
`an excited state, and
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`a plurality of solubilizing functionalities; and
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`(b) one or more second optically active units that can
`receive energy from the excited state of the first optically
`active unit;
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`said aggregation sensor comprising at least three first
`optically active units per second optically active unit;
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`4
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`wherein the second optically active unit is grafted to the
`conjugated polymer.
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`Ex. 1001, 37:45–60.
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` The Asserted Grounds of Unpatentability
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`Petitioner challenges the patentability of claims 1–3, 6–12, 14–17, and
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`19 of the ’673 patent based on the following grounds:
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`References
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`Yang1 and Wang2
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`Statutory
`Basis
`§ 103(a)
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`Claims Challenged
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`1, 3, 15, 16, 19
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`Yang, Wang, and the
`Handbook3
`Yang, Wang, and Inganas4
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`§ 103(a)
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`2, 6
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`§ 103(a)
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`7–12, 14
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`See Pet. 18. Petitioner relies on the Declaration of Kirk S. Schanze, Ph.D.
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`(Ex. 1002)5 to support its asserted grounds of unpatentability. Patent Owner
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`disputes that Petitioner’s asserted grounds render any of the challenged
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`claims unpatentable. See generally Prelim. Resp. Patent Owner relies on
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`the Declaration of Dwight Seferos, Ph.D. (Ex. 2008).
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`1 Yang et al., High-Efficiency Saturated Red-Emitting Polymers Derived
`from Fluorene and Naphthoselenadiazole, 37 MACROMOLECULES 1211–1218
`(2004) (“Yang”) (Ex. 1003).
`2 Wang et al., Size-Specific Interactions Between Single-and Double-
`Stranded Oligonucleotides and Cationic Water-Soluble Oligofluorenes, 13
`ADV. FUNCT. MATER. 463–467 (2003) (“Wang”) (Ex. 1004).
`3 Haugland, HANDBOOK OF FLUORESCENT PROBES AND RESEARCH
`PRODUCTS, 9th ed., Molecular Probes (2002) (“the Handbook”) (Ex. 1005).
`4 Inganas et al., WO 2003/096016 A1, published Nov. 20, 2003 (“Inganas”)
`(Ex. 1006).
`5 Petitioner includes the letters “TFS” with its exhibit numbers. We do not
`adopt that practice in this decision.
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`III. ANALYSIS
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`We organize our analysis into five sections. First, we discuss the level
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`of ordinary skill in the art. Second, we turn to claim construction. Third, we
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`address Yang’s public accessibility and provide a summary of the asserted
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`references. Fourth, taking account of the arguments and evidence presented,
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`we consider whether the Petition meets the threshold showing for instituting
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`an inter partes review based on obviousness. Fifth, we address Patent
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`Owner’s additional argument that we should exercise our discretion under
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`35 U.S.C. § 314(a) to deny institution based on the district court’s schedule
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`in the co-pending litigation.
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` Level of Ordinary Skill in the Art
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`Petitioner, relying on Dr. Schanze’s testimony, asserts that a person of
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`ordinary skill in the art at the time of the invention of the ’673 patent would
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`have had “knowledge of the scientific literature concerning methods of
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`synthesizing fluorescent conjugated polymers and using these polymers for
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`detecting aggregants.” Pet. 7 (citing Ex. 1002 ¶ 11). In particular, Petitioner
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`asserts,
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`Here, a POSA would typically have had (i) a Ph.D. in Chemistry,
`or 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/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.
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`Id. (citing Ex. 1002 ¶ 12).
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` Patent Owner asserts that a person of ordinary skill in the art would
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`have possessed “a Ph.D. in chemistry or related fields and some experience
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`with fluorescence or, alternatively, a master’s degree in chemistry or related
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`fields and industry experience in the field of biological detection systems
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`and/or the use and design of fluorescent dyes.” Prelim. Resp. 5.
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`The parties’ descriptions of the ordinarily skilled artisan are fairly the
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`same, except for Petitioner’s description additionally recognizing a member
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`of an unspecified multidisciplinary team as a person of ordinary skill in the
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`art. Insofar as that additional description is vague, we decline to adopt it.
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`Instead, for purposes of this decision, we determine that the remaining
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`portion of Petitioner’s description of the level of ordinary skill in the art is
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`sufficiently detailed and one that the current record supports. Thus, we
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`recognize, for purposes of this decision, a person of ordinary skill in the art
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`as one having either a Ph.D. in chemistry, or a related field in the chemical
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`sciences, and having at least about two years of experience in chemical
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`synthesis and application of fluorescent conjugated polymers, or a Master's
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`degree in the same fields with at least about five years of the same
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`experience. We also note that the applied prior art reflects the appropriate
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`level of skill at the time of the claimed invention. See Okajima v. Bourdeau,
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`261 F.3d 1350, 1355 (Fed. Cir. 2001).
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`Further, based on the information presented at this stage of the
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`proceeding, we consider Drs. Schanze and Seferos, qualified to opine from
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`the perspective of an ordinary artisan at the time of the invention. See
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`Ex. 1027 (Dr. Schanze’s curriculum vitae); Ex. 2009 (Dr. Seferos’
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`curriculum vitae).
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` Claim Construction
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`For petitions filed before November 13, 2018, the Board interprets
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`claims in an unexpired patent using the “broadest reasonable construction in
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`light of the specification of the patent.” 37 C.F.R. § 42.100(b) (2016);
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`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016).6
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`“Under a broadest reasonable interpretation, words of the claim must be
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`given their plain meaning, unless such meaning is inconsistent with the
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`specification and prosecution history.” Trivascular, Inc. v. Samuels,
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`812 F.3d 1056, 1062 (Fed. Cir. 2016).
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`Petitioner proposes that we adopt certain district court claim
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`constructions for a number of claim terms. Pet. 14–16. In doing so,
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`Petitioner provides the proposed constructions without any discussion or
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`reference to the specification in support of them. In any event, we determine
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`that no claim term requires express construction for purposes of this
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`decision. See Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803
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`(Fed. Cir. 1999) (“[O]nly those terms need be construed that are in
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`controversy, and only to the extent necessary to resolve the controversy.”).
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` Asserted References
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`Below, we provide a brief summary of the asserted references. Before
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`doing so, however, we address Patent Owner’s argument that Petitioner does
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`not establish sufficiently that Yang is prior art.
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`6 The Office recently changed the claim construction standard the Board
`applies in an inter partes review. See Changes to the Claim Construction
`Standard for Interpreting Claims in Trial Proceedings Before the Patent
`Trial and Appeal Board, 83 Fed. Reg. 51340 (October 11, 2018) (noting that
`the rule applies only to petitions filed on or after November 13, 2018).
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` Public Accessibility of Yang
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`The Federal Circuit has held that “public accessibility” is “the
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`touchstone” in determining whether a reference is a printed publication. In
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`re Hall, 781 F.2d 897, 899 (Fed. Cir. 1986). “A given reference is ‘publicly
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`accessible’ upon a satisfactory showing that such document has been
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`disseminated or otherwise made available to the extent that persons
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`interested and ordinarily skilled in the subject matter or art exercising
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`reasonable diligence, can locate it.” SRI Int’l, Inc. v. Internet Sec. Sys., Inc.,
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`511 F.3d 1186, 1194 (Fed. Cir. 2008) (quoting Bruckelmyer v. Ground
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`Heaters, Inc., 445 F.3d 1374, 1378 (Fed. Cir. 2006)).
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`It is apparent that both parties recognize January 31, 2005, the
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`provisional application filing date, as the earliest priority date for challenged
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`claims of the ’113 patent. See Pet. 11, 13–14 (using January 2005 as a
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`reference point for what was known in the art); Ex. 1002 ¶¶ 3, 13
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`(Petitioner’s declarant describing the state of the art before January 31,
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`2005); Prelim. Resp. 5 (stating “the 113 patent’s earliest priority date of
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`January 31, 2005”). Petitioner asserts that Yang is prior art under 35 U.S.C.
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`§ 102(b), contending that it was published on January 16, 2004. Pet. 17. In
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`support of that assertion, Petitioner notes that the journal article includes a
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`statement that it was “Published on Web 01/16/2004.” Id. n.3; Ex. 1003,
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`1211. Petitioner additionally relies upon the testimony of Dr. Schanze who
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`confirms that date “refers to what was a common practice in 2004, and is
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`still common today, the publication of an article on a journal’s website prior
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`to the article appearing in the print version of the journal.” Ex. 1002 ¶ 67.
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`According to Dr. Schanze, a person of ordinary skill in the art “would have
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`understood that this web publication date was the day the Yang reference
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`was made publicly available.” Id.
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`Patent Owner disagrees and asserts that “[t]he Yang article published
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`no earlier than February 24, 2004,” based upon date provided on the cover of
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`the journal, along with the “Volume” and “Number” indications for the
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`journal issue. Prelim. Resp. 5–7. Patent Owner notes also that the cover
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`includes a date stamp by an unidentified library that the journal article was
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`received on February 26, 2004. Id. at 6. Regarding the web publication
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`information appearing in the article, Patent Owner asserts that Petitioner
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`“did not affirmatively assert (nor could it) that exhibit TFS1003—the only
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`version of the Yang article [Petitioner] relies on as prior art—was itself
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`disseminated or otherwise made available to interested relevant artisans
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`before February 24, 2004.” Id. at 8. Additionally, Patent Owner asserts that
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`Petitioner “has not provided any documentary evidence that a document
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`dated January 16, 2004 contained the same disclosure as the Yang article
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`used as [Ex.] 1003.” Id. at 8–9. According to Patent Owner, the facts here
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`align with those in Pfizer, Inc. v. Biogen, Inc., Case IPR2017-01166, Paper 9
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`(PTAB Nov. 13, 2017), wherein the Board determined that Petitioner’s
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`evidence was insufficient to establish, for purposes of the decision on
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`institution, the public accessibility of an asserted reference. Id. at 7–9.
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`Further, Patent Owner challenges Dr. Schanze’s testimony, asserting that it
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`is “unsupported and conclusory.” Id. at 10.7
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`7 Patent Owner asserts also that Yang is not available as prior art under
`35 U.S.C. § 102(a) based upon a contention that the inventors of the ’673
`patent reduced to practice their invention prior to Yang’s critical date.
`Prelim. Resp. 5–6, 12–17. We do not address that contention in this
`Decision, as Petitioner asserts only that Yang is § 102(b) prior art.
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`Having considered the arguments and the evidence, we find that
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`Petitioner has made a threshold showing that Yang was publicly accessible
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`as a printed publication prior to the effective filing date of the ’673 patent.
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`To begin, we note that the facts involved here are distinguishable from those
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`discussed in IPR2017-01166. The institution decision in that case involved
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`a split panel. In the majority opinion, the Board determined that “none of
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`the evidence proffered by Petitioner, either alone or in combination, suggests
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`that the Rituxan Label was disseminated or otherwise made available to
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`ordinarily skilled artisans exercising reasonable diligence prior to the critical
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`date for the [patent at issue].” IPR2017-01166, Paper 9, 12. Such evidence
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`is not missing here. Yang is an article in the Macromolecules journal.
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`Ex. 1003, 2. The journal states that it is a publication of The American
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`Chemical Society that is published biweekly. Id. Unlike with the Rituxan
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`label at issue in IPR2017-01166, Petitioner has identified on the face of the
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`article a disclosure by the publisher that the article was “Published on Web
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`01/16/2004.” Pet. 17 (citing Ex. 1003). Indeed, the exhibit includes the
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`journal page describing its “Web Edition,” stating that “[t]his journal is
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`available to subscribers via the Internet.” Ex. 1003, 2. Subscribers may be
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`individual members, student members, or institutional customers, e.g.,
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`libraries. See id. at “2004 Subscription and Ordering Information.” Thus,
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`based on the current record, we find that Yang, on its face, provides
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`evidence suggesting that the same disclosure was available on the internet to
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`subscribers on January 16, 2004.
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`Moreover, Petitioner provides persuasive testimonial evidence to
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`support finding that Yang was made available to the extent that persons
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`interested and ordinarily skilled in the subject matter or art exercising
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`reasonable diligence, could access it on the web publication date. SRI Int’l,
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`Inc., 511 F.3d at 1194. Based on the current record, we credit Dr. Schanze’s
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`testimony regarding the asserted common practice of publishing an article
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`on a journal’s website prior to the dissemination of the print version of the
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`journal. Ex. 1002 ¶ 67. According to Dr. Schanze, a person of skill in the
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`art would have understood the disclosed web publication date to be the day
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`that Yang was made publicly available. Id. We find that Dr. Schanze is in a
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`unique position to address the web publication practice of the
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`“Macromolecules” journal, as he is “currently an editor for journals
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`published by the American Chemical Society (ACS), the publisher of
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`‘Macromolecules,’” and he affirms that he is “familiar with the ACS’s
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`publication policy in 2004.” Id. ¶ 68. In particular, we credit Dr. Schanze’s
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`testimony that (a) articles were published on the “Macromolecules” website
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`as of their web publication date, and are featured at the top of the webpage
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`for the web publication section, and (b) subscribers to the “Macromolecules”
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`journal receive email notifications of new articles appearing in the web
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`publications sections of the journal website when new publications are
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`posted. Id. Further, Dr. Schanze explains that as an editor of ACS journals,
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`he was aware that the publisher would inform article authors that the web
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`publication date is the date at which their article is considered to be
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`published. Id. at ¶ 69. At this stage in the proceeding, we find no reason to
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`question the veracity of Dr. Schanze’s testimony in this regard.
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`Accordingly, based on the foregoing, we determine that Petitioner has
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`made a sufficient threshold showing that Yang was publicly accessible on
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`January 31, 2004, and is, therefore, recognized as prior art to the ’673 patent
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`under §102(b).
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` Yang (Ex. 1003)
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`Yang is a journal article discussing the synthesis of a “variety of novel
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`light-emitting copolymers derived from 9,9-dioctylfluorene (DOF) and
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`2,1,3-naphthozoselenadiazole (NSeD).” Ex. 1003, Abstract. The polymers
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`are “soluble in common organic solvents and highly fluorescent in solid
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`state.” Id. Yang explains that “polymer light-emitting diodes (PLEDs) have
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`attracted considerable interest because of their potential application in flat
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`panel displays.” Id. at 1211. According to Yang, “[i]t is believed that PLED
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`technology is one of the most promising for next generation large-area flat
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`panel displays.” Id. Yang explains that “[s]ignificant efforts have been
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`made to tune color to longer wavelength for fluorene-based polymers,” and
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`that “[c]ompared with a high-efficiency green polyfluorene emitter reported
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`in the scientific literature, the polymer emitter with saturated red emission
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`remains a great challenge.” Id. Yang further discloses that emission color
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`of polyfluorenes may be tuned over an entire visible region by incorporating
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`narrow band-gap comonomer into the polyfluorene backbone. Id.
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`Yang describes synthesizing its novel copolymers using the
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`palladium-catalyzed Suzuki coupling method. Id. at 1211–1212. Yang
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`teaches that the “2,1,3-naphthoselenadizole unit in the copolymer is isolated
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`from both sides by fluorene host segment functions as a powerful exciton
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`trap which allows efficient intramolecular energy transfer from the fluorene
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`segment to the NSeD unit.” Id. at 1212. Yang reports that “EL
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`[electroluminescence] emission from [the fluorene] segment was completely
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`quenched at very low NSeD content (0.5%). Saturated red emission at the
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`maximum wavelength of 657 nm was obtained.” Id.
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` Wang (Ex. 1004)
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`Wang is a journal article discussing an “improved synthetic approach”
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`for developing “molecules provid[ing] a size-specific series of water-soluble
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`oligofluorene molecules with increasing numbers of repeat units to model
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`the interactions between cationic conjugated polymers and DNA.”
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`Ex. 1004, Abstract. Wang teaches that “[c]onjugated polymers can be used
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`as the optical platform in fluorescent chemical and biological sensors.” Id.
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`at 463. Wang states that “[s]olubility in water is essential for interfacing
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`with biological substrates such as proteins and DNA, and this property is
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`achieved by attaching charged functionalities as pendant groups on the
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`conjugated backbone.” Id. Wang describes how various phenomena in
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`complex biological mixtures allow for rational design of quantitative
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`conjugated polymer-based DNA assays. Id. For example, Wang states,
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`“[i]n the case of conjugated polymers, it is likely that aggregation of the
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`fluorophores within the vicinity of DNA influences their optical properties
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`by mechanisms such as relaxation or contraction of the polymer secondary
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`structure, self-quenching, and photoinduced charge transfer to the DNA
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`bases.” Id.
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` The Handbook (Ex. 1005)
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`Chapter 1 of the Handbook discusses fluorophores and their amine-
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`reactive derivatives. Ex. 1005, Table of Contents. Section 1.2 of that
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`chapter describes kits for labeling proteins and nucleic acids with a
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`fluorescent dye. Id. at 14. In particular, the Handbook describes three
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`nucleic acid labeling kits: ARES DNA Labeling Kits, Alexa Fluor
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`Oligonucleotide Amine Labeling Kits, and ULYSIS Nucleic Acid Labeling
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`Kits. Id. at 18.
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`Inganas is a PCT Application directed to “methods for detection of
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`biomolecular interactions through the detection of alterations of the intra-
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`and inter-chain processes in materials based on zwitterionic conjugated
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`polyelectrolytes.” Ex. 1006, 1:6–8. Inganas explains that conjugated
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`polymers such as poly(thiophene) and poly(pyrrole) are useful as biosensors
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`because they are “sensitive to very minor perturbations, due to amplification
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`by a collective system response.” Id. at 1:15–18. Inganas states that such
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`use of conjugated polymers requires that they are “compatible with aqueous
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`environment.” Id. at 1:20–21. Inganas explains that this may be
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`accomplished by making conjugated polyelectrolytes. Id. at 1:21–23.
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`“[T]he polyelectrolyte comprises copolymers or homopolymers of
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`thiophene, pyrrole, aniline, furan, phenylene, vinylene or their substituted
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`forms, and preferably the conjugated polyelectrolyte has one or more
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`zwitterionic side chain functionalities.” Id. at 3:1–4.
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` Petitioner’s Challenges to the ’673 Patent
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`We now consider whether the Petition meets the threshold showing
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`for instituting an inter partes review based on obviousness. “An
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`obviousness determination requires that a skilled artisan would have
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`perceived a reasonable expectation of success in making the invention in
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`light of the prior art.” Amgen, Inc. v. F. Hoffman–La Roche Ltd., 580 F.3d
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`1340, 1362 (Fed. Cir. 2009). “The reasonable expectation of success
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`requirement refers to the likelihood of success in combining references to
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`meet the limitations of the claimed invention.” Intelligent Bio-Sys, Inc. v.
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`Illumina Cambridge Ltd., 821 F.3d 1359, 1367 (Fed. Cir. 2016). “[O]ne
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`must have a motivation to combine accompanied by a reasonable
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`expectation of achieving what is claimed in the patent-at-issue.” Id.
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` Asserted Obviousness over Yang and Wang
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`Petitioner asserts that claims 1, 3, 15, 16, and 19 of the ’673 patent
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`would have been obvious over the combination of Yang and Wang. Pet. 18–
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`43. Patent Owner disagrees. Prelim. Resp. 17–47.
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`(a) The parties’ assertions
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`Petitioner asserts that “Yang and Wang teach all the elements of claim
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`1.” Pet. 18. According to Petitioner, Yang teaches a conjugated copolymer
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`comprising a plurality of first units, i.e., 9,9-dioctylfluorene monomers,
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`forming a conjugated system (PFO), and one or more second units, NSeD.
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`Id. at 19–20 (citing Ex. 1002 ¶¶ 70, 73–75; Ex. 1003, 3:1:2–4:2:1).
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`Petitioner and Dr. Schanze assert that a person of skill in the art would have
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`understood that the fluorene units are optically active, absorb light at a first
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`absorption wavelength, 390 nm, and form an exciton. Id. at 21–22 (citing
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`Ex. 1003, 4:2:2, 5:Table 2 and Fig. 1, 7:Table 4; Ex. 1002 ¶ 78). Petitioner
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`and Dr. Schanze further assert that Yang’s NSeD unit is also optically active
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`and “functions as a powerful exciton trap which allows efficient
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`intramolecular energy transfer from the fluorene segment to the NSeD unit.”
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`Id. at 22 (quoting Ex. 1003, 4:1:1, 5:2:2, 6:1:1; citing Ex. 1002 ¶ 79).
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`Petitioner asserts also that Yang discloses that its PFO-NSeD copolymers
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`have at least three first optically active units per second optically active unit,
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`as “[t]he comonomer ratios of PFO to NSeD are 99.9:0.1, 99.5:0.5, 99:1,
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`98:2, 95:5, and 85:15.” Id. at 23 (quoting Ex. 1003, 4:1:3). Petitioner
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`additionally asserts that in Yang, the NSeD is grafted to the conjugated
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`polymer. Id. at 24–25 (citing Ex. 1003, 4:Scheme 2; Ex. 1002 ¶¶ 70, 81).
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`Petitioner relies on both Yang and Wang as each teaching aggregation
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`sensors soluble in a polar medium comprising conjugated polymers, with the
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`conjugated polymers comprising a plurality of solubilizing functionalities.
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`Id. at 24–30 (citing Ex. 1002 ¶¶ 82–89; Ex. 1003, 4:1:3, 5:2:2, 6:1:1, 7:Fig.
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`3(b); Ex. 1004 Abstract, 3:1:1–3:1:2, 5:1:1–5:1:3, 5:Fig. 1). However,
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`Petitioner explains that Yang’s conjugated polymers are not water-soluble,
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`whereas Wang’s conjugated polymers are water-soluble. Id. at 28–29.
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`Further, as Yang describes using its conjugated polymers in flat panel
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`displays and not as biosensors, Ex. 1003, 1212, Petitioner relies upon Wang
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`as disclosing using oligofluorenes to detect unlabeled DNA by observing
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`changes in the optical properties of the oligofluorene when they bind and
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`aggregate in the vicinity of DNA. Pet. 27, 32–34 (citing Ex. 1004, 3:1:1–2,
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`5:1:3, 5:Fig. 1, 5:Fig. 2; Ex. 1002 ¶¶ 85–86, 95). Petitioner asserts that
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`“Wang’s system detects unlabeled DNA by observing quenching of
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`oligofluorene’s fluorescence (i.e., decrease in emission intensity).” Id. at 32
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`(citing Ex. 1004, 5:Fig. 1, 5:Fig. 2; Ex. 1002 ¶ 95). According to Petitioner
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`and Dr. Schanze, that method of detection is “not very practical or reliable
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`when a sample contains a small amount of an analyte, because they require
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`equipment sensitive enough to detect minor changes in emission.” Id.
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`(citing Ex. 1002 ¶ 95).
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`Petitioner asserts that Yang’s copolymers, on the other hand, show
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`color changes when aggregated. Pet. 32. For example, Petitioner asserts
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`that “NSeD emission in Yang’s PFO-NSeD5 ‘increased dramatically’ when
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`concentrated in solution,” resulting in “an increase in red emission, while
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`diminishing violet emission (albeit not completely).” Id. (quoting Ex. 1003,
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`5:2:2; citing id. at 7:Fig. 3; Ex. 1002 ¶ 96). Petitioner asserts that in the
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`solid state, the color change was enhanced, with violet emission
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`disappearing completely. Id. (citing Ex. 1003, 6:1:1, 7:Fig. 3). Petitioner
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`asserts that a person of ordinary skill in the art “would have understood that
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`Yang’s copolymers offered unique optical advantages over Wang’s
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`oligofluorenes vis-à-vis their response to aggregation.” Id. at 33.
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`Petitioner further asserts that because Wang teaches “[s]olubility in
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`water is essential for interfacing [conjugated polymers] with biological
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`substrates such as proteins and DNA,” Pet. 34 (quoting Ex. 1004, 3:1:1) a
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`person of ordinary skill in the art would have had a reason to modify Yang’s
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`copolymers to be water-soluble to allow their use in Wang’s system. Id.
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`(citing Ex. 1002 ¶ 101). According to Petitioner and Dr. Schanze, a skilled
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`artisan would have done so in the same manner Wang describes, i.e.,
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`attaching Wang’s cationic functionalities onto Yang’s fluorene monomers
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`prior to combining them with NSeD. Id. at 34–36 (citing Ex. 1002 ¶¶ 102–
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`109).
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`Petitioner and Dr. Schanze further assert that the skilled artisan would
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`have had a reasonable expectation of successfully preparing Yang’s
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`copolymers comprising Wang’s solubilizing functionalities because “Wang
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`and Yang teach chemical routes for attaching two solubilizing functionalities
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`to each fluorene monomer at position 9 of fluorene: octane (Yang) and
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`trimethylaminehexane (Wang).” Ex. 1002 ¶ 106 (citing Ex. 1004,
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`4:Scheme 2; Ex. 1003, 4:1:2–4:2:1); Pet. 36. Additionally, Petitioner asserts
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`that a person of ordinary skill in the art would have had