Trials@uspto.gov
`571-272-7822
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` Paper 8
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` Date: October 4, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`HOLOGIC, INC.,
`Petitioner,
`
`v.
`
`ENZO LIFE SCIENCES, INC.,
`Patent Owner.
`
`
`
`Case IPR2016-00820
`Patent 7,064,197 B1
`
`
`
`
`Before MICHAEL J. FITZPATRICK, ZHENYU YANG, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`
`
`FITZPATRICK, Administrative Patent Judge.
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`571-272-7822
`
`
`
`
`
`
`
`
`
`
`
` Paper 8
`
`
` Date: October 4, 2016
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`HOLOGIC, INC.,
`Petitioner,
`
`v.
`
`ENZO LIFE SCIENCES, INC.,
`Patent Owner.
`
`
`
`Case IPR2016-00820
`Patent 7,064,197 B1
`
`
`
`
`Before MICHAEL J. FITZPATRICK, ZHENYU YANG, and
`CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
`
`
`
`FITZPATRICK, Administrative Patent Judge.
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`IPR2016-00820
`Patent 7,064,197 B1
`
`INTRODUCTION
`
`I.
`Petitioner, Hologic, Inc., filed a Petition to institute an inter partes
`review of claims 1, 6, 8, 9, 12–16, 27, 31–34, 38, 41, 61–64, 68–70, 72–74,
`78, 79, 100, 101, 191–195, 212, 213, 218, 219, 222, 225–227, 230, 233, and
`236 of U.S. Patent No. 7,064,197 B1 (Ex. 1001, “the ’197 patent”) pursuant
`to 35 U.S.C. § 311(a). Paper 1 (“Pet.”). Patent Owner, Enzo Life Sciences,
`Inc., filed a Preliminary Response pursuant to 35 U.S.C. § 313. Paper 7
`(“Prelim. Resp.”).
`
`We have authority to determine whether to institute an inter partes
`review. 35 U.S.C. § 314(b); 37 C.F.R. § 42.4(a). Upon consideration of the
`Petition, and for the reasons explained below, we determine that the
`information presented shows a reasonable likelihood that Petitioner would
`prevail with respect to at least one of the claims challenged. See 35 U.S.C.
`§ 314(a). We grant the Petition to institute an inter partes review.
`
`A. Related Matters
`Petitioner has filed an additional petition to institute an inter partes
`review of the ’197 patent in which it challenges other claims of the patent.
`See IPR2016-00822.
`
`The parties identify the following lawsuits as involving the ’197
`patent: Enzo Life Sciences, Inc. v. Hologic, Inc., No. 1:15-cv-271 (D. Del.);
`Enzo Life Sciences, Inc. v. Siemens Healthcare Diagnostics, Inc., No. 1:12-
`cv-505 (D. Del.); Enzo Life Sciences, Inc. v. Affymetrix, Inc., No. 1:12-cv-
`433 (D. Del.); Enzo Life Sciences, Inc. v. Agilent Technologies Inc., No.
`1:12-cv-434 (D. Del.); Enzo Life Sciences, Inc. v. Illumina Inc., No. 1:12-cv-
`
`2
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`435 (D. Del.); Enzo Life Sciences, Inc. v. Abbott Laboratories et al., No.
`1:12-cv-274 (D. Del.); Enzo Life Sciences, Inc. v. Becton Dickinson and
`Company et al., No. 1:12-cv-275 (D. Del.); Enzo Life Sciences, Inc. v. Life
`Technologies Corp., No. 1:12-cv-105 (D. Del.); and Enzo Life Sciences, Inc.
`v. Roche Molecular Systems Inc. et al., No. 1:12-cv-106 (D. Del.). Pet. 2–3;
`Paper 6, 1–2.
`
`B. The ’197 Patent
`
`The ’197 patent relates generally to the detection of genetic material
`by polynucleotide probes. Ex. 1001, 1:23–24. The ’197 patent refers to the
`material to be detected as an analyte. Id. at 1:37–39. An analyte may be
`present in a biological sample such as a clinical sample of blood, urine,
`saliva, etc. Id. at 5:47–50. If an analyte of interest is present in a biological
`sample, it is fixed, according to the invention of the ’197 patent, in
`hybridizable form to a solid support. Id. at 5:58–60. The ’197 patent states
`that it is preferred, and all of the challenged claims require, that the solid
`support be non-porous. Id. at 6:2–6; e.g., id. at 15:51–53 (claim 17 reciting
`a “non-porous solid support”).
`
`Chemically-labeled probes are then brought into contact with
`the fixed single-stranded analytes under hybridizing conditions.
`The probe is characterized by having covalently attached to it a
`chemical label which consists of a signaling moiety capable of
`generating a soluble signal. Desirably, the polynucleotide or
`oligonucleotide probe provides sufficient number of nucleotides
`in its sequence, e.g., at least about 25, to allow stable
`hybridization with the complementary nucleotides of the
`analyte. The hybridization of the probe to the single-stranded
`analyte with the resulting formation of a double-stranded or
`duplex hybrid is then detectable by means of the signalling
`
`3
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`moiety of the chemical label which is attached to the probe
`portion of the resulting hybrid. Generation of the soluble signal
`provides simple and rapid visual detection of the presence of
`the analyte and also provides a quantifiable report of the
`relative amount of analyte present, as measured by a
`spectrophotometer or the like.
`Id. at 6:15–32.
`
`C. The Challenged Claims
`
`Petitioner challenges claims 1, 6, 8, 9, 12–16, 27, 31–34, 38, 41, 61–
`64, 68–70, 72–74, 78, 79, 100, 101, 191–195, 212, 213, 218, 219, 222, 225–
`227, 230, 233, and 236. Pet. 1. Of the challenged claims, claims 1, 6, 8, 9,
`12–15, and 27 are independent. The remainder of the challenged claims all
`depend directly from at least one of the challenged independent claims, with
`several of them in multiple dependent form.
`
`Claim 1 is illustrative and reproduced below.
`1.
`A non-porous solid support comprising one or
`more amine(s), hydroxyl(s) or epoxide(s) thereon, wherein at
`least one single-stranded nucleic acid is fixed or immobilized in
`hybridizable form to said non-porous solid support via said one
`or more amine(s), hydroxyl(s) or epoxide(s).
`
`
`
`4
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`D. Asserted Grounds of Unpatentability
`
`Petitioner asserts the following grounds of unpatentability:
`Basis1
`References
`Claims Challenged
`Fish (Ex. 1006)2
`§ 102(b)
`1, 6, 8, 9, 12–16, 27, 31–
`34, 41, 61–63, 68–70,
`72–74, 79, 100, 191–194,
`212, 213, 219, 222, 225–
`227, 230, 233, and 236
`31, 64, 68, 101, 192, and
`195
`38, 78, and 218
`
`§ 103(a)
`
`§ 103(a)
`
`§ 102(a)
`and (b)
`
`§ 103(a)
`
`1, 6, 8, 9, 12–15, 27, 31,
`32, 34, 61–63, 68–70, 72,
`74, 79, 100, 191–193,
`194, 213, 219, 226, 227,
`and 236
`33, 41, 73, 212, 225, and
`233
`
`Fish
`
`Fish and Gilham
`(Ex. 1019)3
`VPK (Ex. 1008)4
`
`VPK and Metzgar
`(Ex. 1009)5
`
`
`1 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29, took
`effect on March 18, 2013. Because the application from which the ’197
`patent issued was filed before that date, our citations to 35 U.S.C. §§ 102
`and 103 are to their pre-AIA version.
`2 Falk Fish, et al., “A Sensitive Solid Phase Microradioimmunoassay For
`Anti-Double Stranded DNA Antibodies,” Arthritis and Rheumatism,
`Vol. 24, No. 3, 534–43 (March 1981).
`3 P. T. Gilham, “Immobilized Polynucleotides and Nucleic Acids,”
`Immobilized Biochemicals and Affinity Chromatography, 173–85 (1974).
`
`4 A. C. Van Prooijen-Knegt, et al. “In Situ Hybridization of DNA Sequences
`in Human Metaphase Chromosomes Visualized by an Indirect Fluorescent
`Immunocytochemical Procedure,” Experimental Cell Research, Vol. 141,
`397–407 (Oct. 1982).
`
`5
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`Basis1
`§ 103(a)
`
`References
`Noyes (Ex. 1007),6 VPK,
`and Ramachandran
`(Ex. 1028)7
`Pet. 6–7; see also id. at 40 (asserting that VPK is prior art under § 102(a) as
`well as § 102(b)).
`
`Claims Challenged
`16, 38, 64, 78, 101, 195,
`218, 222, and 230
`
`As an initial matter, we acknowledge Patent Owner’s assertion that
`“Petitioner failed to present any evidence” that its non-patent references (i.e.,
`Fish, Gilham, VPK, Noyes, and Ramachandran) “were publicly accessible
`printed publications.” Prelim. Resp. 6. We disagree, and find on this record
`that Petitioner has made a sufficient showing that each of these references
`qualify as prior art printed publications. For example, Fish appears to be an
`article from the journal Arthritis and Rheumatism and bears a “March 1981”
`publication date on the cover of the volume as well as the cover page of the
`article. Ex. 1006, cover page and 534. Gilham appears to be an article
`published in a book titled Immobilized Biochemicals and Affinity
`Chromatography, which includes a copyright date of 1974 and an indication
`that it contains most of the papers presented in a “Symposium on Affinity
`Chromatography and Immobilized Biochemicals” held November 7–9,
`1973. Ex. 1019, second page after cover (“Library of Congress Cataloging
`
`
`5 U.S. Patent No. 3,572,892, issued Mar. 30, 1971.
`6 Barbara E. Noyes, et al., “Nucleic Acid Hybridization Using DNA
`Covalently Coupled to Cellulose,” Cell, vol. 5, 301–10 (July 1975).
`7 K. B. Ramachandran, et al., “Effects of Immobilization of the Kinetics of
`Enzyme-Catalyzed Reactions. I. Glucose Oxidase in a Recirculation Reactor
`System,” Biotechnology and Bioengineering, Vol. XVIII, 669–84 (1976).
`
`6
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`in Publication Data”). VPK appears to be an article from the journal
`Experimental Cell Research and is dated October 1982. Ex. 1008, cover
`page. Noyes appears to be an article from the journal Cell and is dated July
`1975. Ex. 1007, 301. Finally, Ramachandran appears to be an article from
`the journal Biotechnology and Bioengineering and is dated 1975. Thus, each
`of these references bears a date prior to the earliest possible effective filing
`date for the challenged claims (i.e., Jan. 27, 1983). See Ex. 1001, 1:19; 35
`U.S.C. § 120. Moreover, the references are either journal articles or excerpts
`from a book, and thus appear to have been publicly disseminated. Petitioner
`has made sufficient showing that these documents qualify as prior art printed
`publications. After institution, Patent Owner may, if it chooses to do so,
`continue to challenge the sufficiency or admissibility of the evidence. See
`35 U.S.C. § 311(b); 37 C.F.R. § 42.64(b).
`
`II. ANALYSIS
`
`A. Claim Construction
`
`“A claim in an unexpired patent that will not expire before a final
`written decision is issued shall be given its broadest reasonable construction
`in light of the specification of the patent in which it appears.” 37 C.F.R.
`§ 42.100(b). Pursuant to that standard, the claim language should be read in
`light of the specification, as it would be interpreted by one of ordinary skill
`in the art. In re Suitco Surface, Inc., 603 F.3d 1255, 1260 (Fed. Cir. 2010).
`Thus, we generally give claim terms their ordinary and customary meaning.
`See In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007) (“The
`ordinary and customary meaning is the meaning that the term would have to
`a person of ordinary skill in the art in question.” (internal quotation marks
`7
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`Patent 7,064,197 B1
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`omitted)).
`
`Our construction of the challenged claims is based on the current
`record and, thus, could change during trial, in light of new arguments and
`evidence.
`
`1. “non-porous solid support”
`All of the independent claims that are challenged recite a “non-porous
`solid support.” Neither party proposes an express construction. See Pet. 12
`(Petitioner arguing that it should be given its ordinary meaning in the art);
`see generally Prelim. Resp. In a related lawsuit, the court construed “non-
`porous” to mean “having no pores” and “solid support” to mean a “solid
`structure.” Ex. 1010, 5–6. The court’s constructions accurately restate what
`the claim language means in the context of the ’197 patent. However, we
`find it unnecessary to expressly construe this claim language. We give
`“non-porous solid support” its ordinary meaning, in light of the
`specification, as it would be interpreted by one of ordinary skill in the art.
`
`2. “fixed or immobilized in hybridizable form”
`All of the independent claims that are challenged recite “fixed or
`immobilized [] in hybridizable form.”
`
`The parties agree that “fixed or immobilized” means “bound.”
`Pet. 11; Prelim. Resp. 13 n.3; see also Ex. 1010, 13–15 (Markman order
`applying same construction). We give it the agreed-upon meaning.
`
`The parties agree that “hybridizable form” means “capable of binding
`
`8
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`through Watson-Crick base pairing.” Pet. 14 (citing Ex. 1001, 2:22–34);
`Prelim. Resp. 128; see also Ex. 1010, 5 (Markman order applying same
`construction). We give it the agreed-upon meaning.
`
`B. Ground 1: Anticipation by Fish
`
`Petitioner asserts that claims 1, 6, 8, 9, 12–16, 27, 31–34, 41, 61–63,
`68–70, 72–74, 79, 100, 191–194, 212, 213, 219, 222, 225–227, 230, 233,
`and 236 are anticipated by Fish. Pet. 6.
`
`Anticipation requires that “each and every element as set forth in the
`claim is found, either expressly or inherently described, in a single prior art
`reference.” Verdegaal Bros., Inc. v. Union Oil Co. of Cal., 814 F.2d 628,
`631 (Fed. Cir. 1987).
`
`1. Disclosure of Fish
`Fish describes a “sensitive solid phase microradioimmunoassay . . .
`for measurement of antidouble stranded DNA (dsDNA) antibodies.”
`Ex. 1006, Abstract. Fish notes “the capacity of poly-L-lysine (PLL) to
`facilitate the binding of pure dsDNA to plastic surfaces.” Id. Fish describes
`an experiment in which “[t]wenty-five microliter aliquots of the PLL
`solution were introduced into each well of a V-shaped polyvinyl
`microtitration tray.” Id. at 536, left col. ¶1.9 Synthetic double-stranded
`
`
`8 Patent Owner’s construction additionally adds that the Watson-Crick base
`pairing would be “to a complementary nucleic acid sequence.” Prelim.
`Resp. 12. This additional language, however, is superfluous, as it merely
`describes what Watson-Crick base pairing inherently requires.
`9 Unless otherwise noted, our citations to paragraphs of non-patent
`
`
`9
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`DNA (“dsDNA”) in the form of a double-stranded copolymer of
`deoxyadenosine and deoxythymidine (“poly dA–dT”) was introduced into
`the wells of alternating rows, and certain washing and incubation steps were
`performed. Id.
`
`Fish next describes the same procedure but using single stranded
`DNA (“ssDNA”) either in the form of: (1) a mixture of synthetic
`homopolymers of deoxyadenosine (“poly-dA”) and deoxycytidine (“poly-
`dC”) or (2) denatured calf thymus DNA. Id. at 536, left col. ¶2; id. at 539,
`Fig. 1 (caption: “PLL treated microtitration wells were coated with various
`preparations of double-stranded and single-stranded DNA.”).
`
`“Half of the nucleic acid coated wells were subjected to nuclease S1
`digestion.” Id. at 538, right col. ¶1; see also id. at 539, Fig. 1. S1 nuclease
`digests ssDNA but not dsDNA. Id. at 538, right col. ¶1. The measured
`attachment/activity of the anti-DNA antibody in the wells is shown in the
`right-hand column of Figure 1 of Fish. Id. at 539, Fig. 1. According to Fish,
`the results demonstrated that:
`
`[N]uclease S1 treatment had no effect on the binding of SLE
`Ig[10] to poly dA–dT coated wells, thus indicating that this DNA
`preparation was indeed wholly double-stranded. On the other
`hand, the binding of [SLE] Ig to heat-denatured DNA was
`almost completely abolished by the enzymatic digestion. This
`positive control for the nuclease S1 activity suggests that single-
`
`references are numbered starting with the first full paragraph of a respective
`page or column.
`10 The anti-DNA antibody employed was plastic systemic lupus
`erythematosus patient serum Immunoglobulin, or SLE Ig. Ex. 1006, 534,
`Abstract.
`
`10
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`Patent 7,064,197 B1
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`stranded nucleic acid, bound to PLL treated plastic, remains
`susceptible to the hydrolytic activity of the enzyme.
`Id. at 538, right col. ¶1.
`
`2. Application of Fish to the Challenged Independent Claims
`The challenged independent claims (namely, claims 1, 6, 8, 9, 12, 13,
`14, 15, and 27) are of similar scope, and none of their differences is material
`in light of the Fish teachings on which Petitioner relies. Accordingly, we
`address explicitly only independent claim 1.11
`
`Independent claim 1 recites, in both the preamble and the body of the
`claim, a “non-porous solid support.” Fish appears to meet this limitation
`because Fish uses microtitration trays that are polyvinvyl (Ex. 1006, 536,
`left col. ¶1), which material is plastic and non-porous according to the
`testimony of Norman Nelson, Ph.D. Ex. 1002 ¶¶38, 40, 68.
`
`Claim 1 recites a “non-porous solid support comprising one or more
`amine(s), hydroxyl(s) or epoxide(s) thereon.” Fish appears to meet this
`
`
`11 Even if the claims were materially different, it would be proper
`nonetheless to address a single claim and, assuming that Petitioner has
`established a reasonable likelihood of prevailing with respect to that claim
`(which Petitioner has), institute on all challenged claims. See 35 U.S.C.
`§ 314(a) (requiring, for institution, “a reasonable likelihood that the
`petitioner would prevail with respect to at least 1 of the claims challenged in
`the petition.”). By Rule, this standard is to be applied on a ground-by-
`ground basis. See 37 C.F.R. § 42.108(c) (“Inter partes review shall not be
`instituted for a ground of unpatentability unless the Board decides that the
`petition supporting the ground would demonstrate that there is a reasonable
`likelihood that at least one of the claims challenged in the petition is
`unpatentable.”).
`
`11
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`limitation because it discloses treating the microtitration tray with PLL (Ex.
`1006, 536, left col. ¶¶1–2), which provides amine groups on the surface of
`the tray. Ex. 1002 ¶42; Ex. 1017, 1, right col. ¶2 (“Non-terminated DNA
`has also been spotted onto amine functionalized surfaces such as PLL.”), 2,
`left col. ¶1 (“PLL, APS and PAMAM all present amine functional groups
`suitable for interaction with DNA.”).
`
`Claim 1 recites “at least one single-stranded nucleic acid.” Fish
`appears to meet this limitation because it discloses wells of ssDNA (i.e., the
`mixture of poly-dA and poly-dC as well as the denatured calf thymus DNA).
`Ex. 1006, 536, left col. ¶¶1–2.
`
`Claim 1 recites that the single-stranded nucleic acid is “fixed or
`immobilized in hybridizable form to said non-porous solid support via said
`one or more amine(s), hydroxyl(s) or epoxide(s).” Fish appears to meet
`these limitations. First, it discloses ssDNA (i.e., the mixture of poly-dA and
`poly-dC as well as the denatured calf thymus DNA) bound to the PLL-
`coated wells of the microtitration tray. Ex. 1006, 536, left col. ¶¶1–2, 539,
`Fig. 1; see also Ex. 1002 ¶53 (Dr. Nelson: “[The amine groups of PLL form
`non-covalent bonds with nucleic acids via ionic interactions between the
`positive charges of the amine groups and the negative charges of the
`phosphate groups in the DNA.”).
`
` Patent Owner argues that the Fish experiment was “not designed to
`determine whether single-stranded nucleic acids bound to PLL-coated
`wells.” Prelim. Resp. 13–14. But, that is not relevant to whether or not Fish
`discloses single-stranded nucleic acids bound to the PLL-coated wells of the
`microtitration tray, which Fish explicitly does. See Ex. 1006, 538, right col.
`12
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`¶1 (stating that “single-stranded nucleic acid” was “bound to PLL treated
`plastic”).
`
`In any event, it appears that the Fish researchers had no need to make
`such a determination because they already knew that ssDNA would bind to
`the PLL-coated wells, as they were relying on such binding to carry out their
`experiment. See Ex. 1006, 536, left col. ¶2 (“Single stranded DNA coated
`trays. A mixture of poly-dA (5 μg/ml) and poly-dC (5 μg/ml) in Tris buffer
`was introduced into PLL-coated microtitration trays as described previously
`[with respect to the synthetic dsDNA].”), 538, right col. ¶1 (“This positive
`control for the nuclease S 1 activity suggests that single-stranded nucleic
`acid, bound to PLL treated plastic, remains susceptible to the hydrolytic
`activity of the enzyme.”).
`
`Petitioner offers additional evidence that the ssDNA binds to the PLL-
`coated wells, as the Fish researchers explicitly recognized. Specifically,
`Petitioner notes that, in Figure 1 of Fish, the ssDNA samples that were
`treated with S1 showed less binding of SLE Ig than identical ssDNA samples
`that were not exposed to S1. Pet. 22–23. Because S1 digests ssDNA, the
`difference in binding proves that there was ssDNA there to be digested. Id.
`at 23.
`
`Petitioner argues that the bound ssDNA in Fish is in “hybridizable
`form” because it “necessarily was capable of binding through Watson Crick
`base pairing.” Pet. 25 (citing Ex. 1002 ¶¶62, 64). In the cited testimony, Dr.
`Nelson testifies that this is so because the bound ssDNA will hybridize when
`complementary DNA is present in appropriate hybridization conditions.”
`Ex. 1002 ¶64.
`
`13
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`“The very essence of inherency is that one of ordinary skill in the art
`would recognize that a reference unavoidably teaches the property in
`question.” Agilent Techs., Inc. v. Affymetrix, Inc., 567 F.3d 1366, 1383 (Fed.
`Cir. 2009). Patent Owner, citing Agilent, argues that Fish does not
`inherently teach ssDNA in hybridizable form, stating:
`
`Whether a given nucleic acid is capable of hybridizing
`depends upon multiple factors, including the type of nucleic
`acid, the type of solid support, the way that the nucleic acid is
`bound to a support, and hybridization conditions. (Ex. 2001
`[declaration of Gregory Buck, Ph.D.] ¶ 72.) In order to
`determine whether a given nucleic acid bound to a solid support
`is capable of hybridization, experimental evidence showing that
`this bound nucleic acid does actually hybridize is necessary.
`(Ex. 2001 ¶ 72.)
`However, Petitioner does not—because it cannot—
`identify any evidence that hybridization actually occurred in
`any of Fish’s experiments.
`Prelim. Resp. 15. Patent Owner’s argument is not commensurate with the
`claim language, which does not require actual hybridization. The claims
`require only that the bound ssDNA be in “hybridizable form.” As the parties
`agree, “hybridizable form” means the ssDNA is capable of binding through
`Watson-Crick base pairing. Petitioner adequately has shown that because
`the bound ssDNA in Fish would hybridize with complementary strands of
`ssDNA under suitable conditions, the bound ssDNA is necessarily capable
`of binding through Watson-Crick base pairing. See Ex. 1002 ¶64.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that independent claims 1, 6, 8, 9, 12, 13, 14, 15, and 27 are anticipated by
`Fish.
`
`14
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`3. Application of Fish to the Challenged Dependent Claims
`Each of claims 16, 31–34, 41, 61–63, 68–70, 72–74, 79, 100, 191–
`194, 212, 213, 219, 222, 225–227, 230, 233, and 236 depends directly from
`at least one of the challenged independent claims. Except with respect to
`claims 3, 68, and 192, Petitioner adequately shows how the additional
`limitations recited in these claims are taught by Fish. See Pet. 30–33.
`
`Each of claims 31, 68, and 192 recites that the fixed or immobilized
`“nucleic acid comprises a nucleic acid sequence complementary to a nucleic
`acid sequence of interest sought to be identified, quantified or sequenced.”
`Petitioner argues that this limitation is met by Fish because it discloses poly-
`dA, which “is complementary to poly-dT, which may be a sequence of
`interest sought to be identified, quantified or sequenced.” Pet. 31 (emphasis
`added). Per Petitioner’s own argument, this additional limitation is not
`satisfied by Fish.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that dependent claims 16, 32–34, 41, 61–63, 69, 70, 72–74, 79, 100, 191,
`193, 194, 212, 213, 219, 222, 225–227, 230, 233, and 236—but not claims
`31, 68, and 192—are anticipated by Fish.
`
`C. Ground 2: Obviousness in View of Fish
`
`Petitioner contends that dependent claims 31, 64, 68, 101, 192, and
`195 would have been obvious over Fish. Pet. 6. In assessing obviousness,
`“the scope and content of the prior art are to be determined; differences
`between the prior art and the claims at issue are to be ascertained; and the
`level of ordinary skill in the pertinent art resolved.” Graham v. John Deere
`
`15
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`IPR2016-00820
`Patent 7,064,197 B1
`
`Co., 383 U.S. 1, 17 (1966).12
`
`Claims 31, 68, and 192 recite that the fixed or immobilized “nucleic
`acid comprises a nucleic acid sequence complementary to a nucleic acid
`sequence of interest sought to be identified, quantified or sequenced.”
`Petitioner’s expert testifies that because it “was well known prior to 1983
`that hybridization of labeled nucleotide sequences to complementary
`sequences can be used to identify, detect, or quantify target (analyte)
`sequences by binding one of the strands to a substrate and introducing
`labeled nucleotide sequences complementary to the bound sequence,” it
`would have been obvious to a person of ordinary skill in the art “that the
`ssDNA immobilized on the microtitration tray wells of Fish can be used to
`detect a complementary sequence of interest, as recited in claims 31, 68, and
`192.” Ex. 1002 ¶78; see also Pet. 36 (citing the same). We find this
`testimony persuasive.
`
` Claims 64, 101, and 195 recite that the fixed or immobilized “nucleic
`acid is RNA.” Petitioner adequately explains how and why a person of
`ordinary skill in the art would have adapted Fish such that the subject matter
`of these claims would have been obvious. Pet. 37.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`
`
`12 Additionally, secondary considerations such as “commercial success, long
`felt but unsolved needs, failure of others, etc., might be utilized to give light
`to the circumstances surrounding the origin of the subject matter sought to
`be patented. As indicia of obviousness or nonobviousness, these inquiries
`may have relevancy.” Graham, 383 U.S. at 17–18. The current record,
`however, lacks such evidence.
`
`16
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`
`that dependent claims 31, 64, 68, 101, 192, and 195 would have been
`obvious over Fish.
`
`D. Ground 3: Obviousness in View of Fish and Gilham
`
`Petitioner contends that dependent claims 38, 78, and 218 would have
`been obvious over Fish and Gilham. Pet. 6. These claims recite “wherein
`said fixation or immobilization to said non-porous . . . solid support is
`covalent.”
`
`Gilham discloses covalently linking polynucleotides to solid matrices.
`Ex. 1019, 173. For example, according to Dr. Nelson, Gilham discloses
`covalent binding of RNA to aminoethylcellulose solid supports through the
`reactivity of the 3'-terminal cis diol moiety of the RNA to the amine group
`of the cellulose support. Ex. 1002 ¶81 (citing Ex. 1019, 174 at Table I
`(covalent binding at the polynucleotide terminal by periodate oxidation of
`3’-terminals of RNA), 175 ¶2). Gilham discloses that “[c]ovalent
`immobilization via the periodate oxidation of the 3'-terminals of
`polynucleotides has also been used for the isolation of complementary
`polynucleotides.” Ex. 1019, 179 ¶1. Gilham goes on to state that such
`immobilized RNA provides “a new approach” to study complementary
`sequences. Id.
`
`Petitioner argues that a person of ordinary skill in the art would have
`been “motivated, with a reasonable expectation of success, to covalently
`bind RNA using the technique described in Gilham on easy-to-use, non-
`porous supports (such as the microtitration plates disclosed in Fish) because
`covalent binding provides a stronger linkage between the immobilized
`nucleic acids and the solid substrate.” Pet. 39. We find this reasoning
`17
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`IPR2016-00820
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`
`adequate.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that dependent claims 38, 78, and 218 would have been obvious over Fish
`and Gilham.
`
`E. Ground 4: Anticipation by VPK
`
`Petitioner contends that claims 1, 6, 8, 9, 12–15, 27, 31, 32, 34, 61–
`63, 68–70, 72, 74, 79, 100, 191–193, 194, 213, 219, 226, 227, and 236 are
`anticipated by VPK.
`
`1. VPK is Prior Art on the Record Presented
`The ’197 patent claims priority to various applications, the oldest two
`being U.S. Patent Application Ser. No. 06/732,374 (“the ’374 application”),
`filed on May 9, 1985, and U.S. Patent Application Ser. No. 06/461,469 (“the
`’469 application”), filed on January 27, 1983. Ex. 1001, 1:8–19. Petitioner
`asserts that VPK, which was published October 1982 (Ex. 1008, cover
`page), is prior art to the challenged claims of the ’197 patent under both 35
`U.S.C. §§ 102(a) and (b). Pet. 39–40.
`
`With respect to whether VPK is prior art under § 102(a), Petitioner
`points out that VPK was published before the earliest filing date in the claim
`of priority, which is the earliest presumed invention date. Id. at 40; see
`Mahurkar v. C.R. Bard, Inc., 79 F.3d 1572, 1577 (Fed. Cir. 1996) (“Had Dr.
`Mahurkar not come forward with evidence of an earlier date of invention,
`the Cook catalog would have been anticipatory prior art under section 102(a)
`because Dr. Mahurkar’s invention date would have been the filing date of
`his patent.”).
`
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`
`With respect to whether VPK is prior art under § 102(b), Petitioner
`argues that the challenged claims are not adequately supported by the ’469
`application and, thus, not entitled under 35 U.S.C. § 120 to the benefit of its
`January 1983 filing date. Pet. 40–45. Accordingly, as Petitioner argues, the
`challenged claims are entitled to an effective filing date no earlier than that
`of the ’374 application, which was filed in May 1985 and more than one
`year after VPK published in October 1982. Id.
`
`In its Preliminary Response, Patent Owner argues that the challenged
`claims are entitled to the benefit of the January 1983 filing date, thereby
`disqualifying VPK as § 102(b) prior art. Prelim. Resp. 37–44. Patent
`Owner does not, however, argue that the claims are entitled to an even
`earlier invention date. Accordingly, on the current record, VPK is prior art
`under § 102(a), see Mahurkar, 79 F.3d at 1577, and we need not decide
`whether VPK is also prior art under § 102(b).
`
`2. Disclosure of VPK
`VPK “describes modifications of [existing] in situ hybridization and
`immunocytochemical procedures, permitting identification of specific DNA
`sequences in human chromosomes by fluorescence microscopy.” Ex. 1008,
`398, left col. ¶1; see also Ex. 1002 ¶93. It discloses binding of human blood
`culture cells with metaphase chromosomes to aminoalkylsilane-treated glass
`slides. Ex. 1008, 398, right col. ¶1, 401, Figs. 2 and 3; see also Ex. 1002
`¶¶89–91. The DNA in the chromosomes is denatured, and the resulting
`ssDNA is then hybridized with RNA. Id. at 399, left col. ¶¶2–3; see also
`Ex. 1002 ¶92.
`
`19
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`3. Application of VPK to the Challenged Independent Claims
`The challenged independent claims (namely, claims 1, 6, 8, 9, 12, 13,
`14, 15, and 27) are of similar scope, and none of their differences is material
`in light of the VPK teachings on which Petitioner relies. Accordingly, we
`address explicitly only independent claim 1.
`
`Independent claim 1 recites, in both the preamble and the body of the
`claim, a “non-porous solid support.” VPK appears to meet this limitation
`because it uses glass slides, which are non-porous solid supports. Ex. 1008,
`398, right col. ¶1; Ex. 1002 ¶88.
`
`Claim 1 recites a “non-porous solid support comprising one or more
`amine(s), hydroxyl(s) or epoxide(s) thereon.” VPK appears to meet this
`limitation because it treats the glass slides aminoalkylsilane, which provides
`alkyamines on the surface of the glass slides. Ex. 1008, 398, right col. ¶¶1–
`2; Ex. 1015, 334; Ex. 1002 ¶89.
`
`Claim 1 recites “at least one single-stranded nucleic acid [that] is
`fixed or immobilized in hybridizable form to said non-porous solid support.”
`VPK appears to meet this limitation because the chromosomes are bound to
`the aminoalkylsilane-treated glass slides and then denatured into ssDNA,
`which is a hybridizable form. Ex. 1008, 398, right col. ¶1, 399, left col.
`¶¶2–3, 401, Figs. 2 and 3; Ex. 1002 ¶¶89–92. Patent Owner argues that
`VPK does not meet this limitation because the chromosomes are not bound
`directly to the aminoalkylsilane-treated glass slides. Prelim. Resp. 45–46.
`Instead, in VPK, the chromosomes are indirectly bound to the slides, as they
`are contained within blood culture cells that are directly
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