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 IPR2016-00822
`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
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` 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 IPR2016-00822
`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
`
`
`
`
`
`
`
`IPR2016-00822
`Patent 7,064,197 B1
`
`INTRODUCTION
`
`I.
`Petitioner, Hologic, Inc., filed a Petition to institute an inter partes
`review of claims 17, 19, 25, 105, 106, 113, 114, 116, 119, 120, 128–131,
`150–152, 154, 178, 180, 185–187, and 189 of U.S. Patent No. 7,064,197 B1
`(Ex. 1001, “the ’197 patent”) pursuant to 35 U.S.C. § 311(a). Paper 3
`(“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 IPR2016-00820.
`
`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-
`435 (D. Del.); Enzo Life Sciences, Inc. v. Abbott Laboratories et al., No.
`
`2
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`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
`moiety of the chemical label which is attached to the probe
`portion of the resulting hybrid. Generation of the soluble signal
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`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 17, 19, 25, 105, 106, 113, 114, 116, 119,
`120, 128–131, 150–152, 154, 178, 180, 185–187, and 189. Pet. 1.
`Independent claims 17, 19, and 25 are illustrative and reproduced below.
`17. An array comprising various single-stranded
`nucleic acids fixed or immobilized in hybridizable form to a
`non-porous solid support.
`19. An array comprising single-stranded nucleic acids
`fixed or immobilized in hybridizable form to a non-porous solid
`support.
`25. An array comprising various single-stranded
`nucleic acids fixed or immobilized in hybridizable form to a
`non-porous solid support having wells or depressions.
`
`All of the remaining claims that are challenged depend directly from
`at least one of independent claims 17, 19, and 25, with several of them in
`multiple dependent form.
`
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`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)
`17, 19, 25, 105, 106, 114,
`116, 119, 128, 129, 131,
`150, 152, 178, 180, 186,
`and 187
`130, 131, 151, and 154
`120 and 189
`
`§ 103(a)
`§ 103(a)
`
`Fish
`Fish, Metzgar (Ex. 1009),3
`and Sato (Ex. 1034)4
`Fish and Gilham
`(Ex. 1019)5
`VPK (Ex. 1008)6 and
`Metzgar
`
`§ 103(a)
`
`113 and 185
`
`§ 103(a)
`
`17, 19, 25, 105, 106, 114,
`119, 120, 128, 129, 131,
`150–152, 178, 180, 186,
`and 189
`
`
`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 U.S. Patent No. 3,572,892, issued Mar. 30, 1971.
`4 Sato et al., “Cell Surface Charge and Cell Division in Escherichia coli
`after X irradiation,” Radiation Research 87, 646–56 (1981).
`5 P. T. Gilham, “Immobilized Polynucleotides and Nucleic Acids,”
`Immobilized Biochemicals and Affinity Chromatography, 173–85 (1974).
`
`6 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)
`
`Claims Challenged
`113, 116, 130, 154, 185,
`and 187
`
`References
`Noyes (Ex. 1007),7 VPK,
`Metzgar, and
`Ramachandran (Ex. 1028)8
`Pet. 6; see also Pet. 29–30 (arguing that Fish anticipates claim 131 despite
`not listing claim 131 in its identification of the ground on page 6 of the
`Petition).
`
`As an initial matter, we acknowledge Patent Owner’s assertion that
`“Petitioner failed to present any evidence” that several of the references
`(namely, Fish, Sato, 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. Sato appears to be
`an article from the journal Radiation Research and bears a publication date
`of 1981. Ex. 1034, 646. 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
`
`
`7 Barbara E. Noyes, et al., “Nucleic Acid Hybridization Using DNA
`Covalently Coupled to Cellulose,” Cell, vol. 5, 301–10 (July 1975).
`8 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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`Immobilized Biochemicals” held November 7–9, 1973. Ex. 1019, second
`page after cover (“Library of Congress Cataloging 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
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`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
`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. “array”
`Each of independent claims 17, 19, and 25 recites an “array.”9 The
`parties agree that “array” should be construed to mean “an orderly grouping
`or arrangement.” Pet 14; Prelim. Resp. 22 (proposing same construction but
`doing so while also construing surrounding claim language); see also
`Ex. 1010, 8 (Markman order applying same construction). We give it the
`agreed-upon meaning.
`
`2. “fixed or immobilized in hybridizable form”
`Each of independent claims 17, 19, and 25 recites “fixed or
`immobilized in hybridizable form.”
`
`The parties agree that “fixed or immobilized” means “bound.” Pet. 9;
`Prelim. Resp. 13 n.2; see also Ex. 1010, 13–15 (Markman order applying
`same construction). We give it the agreed-upon meaning.
`
`
`9 The recitation of “array” appears only in the preambles of these claims.
`Neither party explicitly addresses whether the preambles are limiting or not.
`See, e.g., Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305–
`06 (Fed. Cir. 1999) (preamble may or may not be limiting).
`
`8
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`The parties agree that “hybridizable form” means “capable of binding
`through Watson-Crick base pairing.” Pet. 13 (citing Ex. 1001, 2:22–34);
`Prelim. Resp. 1110; see also Ex. 1010, 5 (Markman order applying same
`construction). We give it the agreed-upon meaning.
`
`3. “non-porous solid support”
`Each of independent claims 17, 19, and 25 recites “a non-porous solid
`support.” Neither party proposes an express construction. See Pet. 11
`(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.
`
`B. Ground 1: Anticipation by Fish
`
`Petitioner asserts that claims 17, 19, 25, 105, 106, 114, 116, 119, 128,
`129, 131, 150, 152, 178, 180, 186, and 187 are anticipated by Fish. Pet. 6,
`29–30.
`
`Anticipation requires that “each and every element as set forth in the
`
`10 Patent Owner’s construction additionally adds that the Watson-Crick base
`pairing would be “to a complementary nucleic acid sequence.” Prelim.
`Resp. 11. This additional language, however, is superfluous, as it merely
`describes what Watson-Crick base pairing inherently requires.
`
`9
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`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. ¶1.11 Synthetic double-stranded
`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 to the entire tray. 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.”).
`
`
`11 Unless otherwise noted, our citations to paragraphs of non-patent
`references are numbered starting with the first full paragraph of a respective
`page or column.
`
`10
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`“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[12] 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-
`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 Independent Claims 17, 19, and 25
`Independent claims 17 and 25 recite “[a]n array comprising various
`single-stranded nucleic acids.” Independent claim 19 recites the same
`language except that it omits the word “various.” Fish discloses such arrays
`because it discloses wells of ssDNA (i.e., the mixture of poly-dA and poly-
`dC as well as the denatured calf thymus DNA) arranged in rows. Ex. 1006,
`536, left col. ¶¶1–2. Patent Owner argues that this limitation (assuming the
`preamble is limiting) is not met by Fish because “a microtitration tray is not
`itself an array.” Prelim. Resp. 22. This argument is not persuasive. Fish
`
`12 The anti-DNA antibody employed was plastic systemic lupus
`erythematosus patient serum Immunoglobulin, or SLE Ig. Ex. 1006, 534,
`Abstract.
`
`11
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`explicitly describes rows of wells on the tray, which are sufficient to
`constitute an orderly grouping or arrangement.
`
`Claims 17 and 19 recite a “non-porous solid support,” and claim 25
`recites “a non-porous solid support having wells or depressions.” Fish
`appears to meet these limitations because Fish uses microtitration trays that
`are polyvinvyl (Ex. 1006, 536), which material is plastic and non-porous
`according to the testimony of Norman Nelson, Ph.D. Ex. 1002 ¶¶41, 42.
`
`Claims 17, 19, and 25 recite that the single-stranded nucleic acids are
`“fixed or immobilized in hybridizable form to said non-porous solid
`support.” Fish appears to meet this limitation because 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. Patent Owner argues that Fish does
`not disclose this limitation because its experiment was “not designed to
`determine whether single-stranded nucleic acids bound to PLL-coated
`wells.” Prelim. Resp. 13. That is not relevant to whether or not Fish
`discloses the limitation, which Fish explicitly does. See Ex. 1006, 538, right
`col. ¶1 (referring to “single-stranded nucleic acid” as “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
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`[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. 20–21. Because S1 digests ssDNA, the
`difference in binding proves that there was ssDNA there to be digested. Id.
`at 21.
`
`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. 22 (citing Ex. 1002 ¶66). 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 ¶66.
`
`“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. 2101
`13
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`[declaration of Gregory Buck, Ph.D.] ¶ 73.) 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. 2101 ¶ 73.)
`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 complimentary strands of
`ssDNA under suitable conditions, the bound ssDNA is necessarily capable
`of binding through Watson-Crick base pairing. See Ex. 1002 ¶66.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that independent claims 17, 19, and 25 are anticipated by Fish.
`
`3. Application of Fish to Dependent Claims 105, 106, 114, 116, 119, 128,
`129, 131, 150, 152, 178, 180, 186, and 187
`
`Each of claims 105, 106, 114, 116, 119, 128, 129, 131, 150, 152, 178,
`180, 186, and 187 depends directly from at least one of independent claims
`17, 19, and 25. As explained below, except with respect to claim 131,
`Petitioner adequately shows how the additional limitations recited in these
`claims are taught by Fish.
`
`Claims 105 and 178 add that “said non-porous solid support
`comprises glass or plastic.” The microtitration tray disclosed by Fish is
`
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`made of polyvinyl (Ex. 1006, 536, col. 1 ¶1), which Dr. Nelson testifies is
`plastic. Ex. 1002 ¶70; see also Ex. 1006, Abstract (implying that plastic is
`used, noting “the capacity of poly-L-lysine (PLL) to facilitate the binding of
`pure dsDNA to plastic surfaces”).
`
`Claim 106 adds that “said non-porous solid support” comprises “a
`plate or plates, a well or wells, a microtiter well or microtiter wells, a
`depression or depressions, a tube or tubes, or a cuvette or cuvettes.”
`Similarly, claim 119 adds that “said non-porous solid support” comprises “a
`well or wells, a microtiter well or microtiter wells, or a depression or
`depressions.” Fish discloses a non-porous solid support that comprises
`wells. Ex. 1006, 536, col. 1 ¶1.
`
`Claims 114 and 186 add that “said fixation or immobilization to said
`non-porous solid support is non-covalent.” Petitioner argues that the binding
`of ssDNA to the PLL-coated wells in Fish is ionic and, thus, non-covalent.
`Pet. 28 (citing Ex. 1002 ¶77). At this stage of the proceeding, we credit Dr.
`Nelson’s testimony to that effect.
`
`Claims 116 and 187 add that “said fixation or immobilization [of the
`single-stranded nucleic acids] is not to a cell fixed in situ to said non-porous
`solid support.” Fish appears to meet this limitation because no cells are
`involved in the microradioimmunoassay discussed therein. See generally
`Ex. 1006.
`
`Claims 128 and 150 add that “said nucleic acids [are] DNA.” Fish
`discloses the use of DNA. See, e.g., Ex. 1006, 539, Fig. 1 (“PLL treated
`microtitration wells were coated with various preparations of double-
`stranded and single-stranded DNA.”).
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`Claims 129 and 152 add that “said single-stranded nucleic acids are
`unlabeled.” Fish appears to meet this limitation because it does not mention
`whether the mixture of poly-dA and poly-dC or the denatured calf thymus
`was labeled or not. See Upsher-Smith Labs., Inc. v. Pamlab, LLC, 412 F.3d
`1319, 1322–23 (Fed. Cir. 2005) (holding that if a reference discloses
`everything a claim affirmatively requires, a prima facie case of anticipation
`exists). Further, Patent Owner has not argued or shown that the ssDNA in
`Fish was labeled.
`
`Claim 131 adds that the fixed or immobilized “nucleic acids comprise
`nucleic acid sequences complementary to nucleic acid sequences 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. 29–30 (emphasis added). Per
`Petitioner’s own argument, this additional limitation is not satisfied by Fish.
`
`Claim 180 adds that the non-porous solid support has been “treated
`with a surface treatment agent, a blocking agent, or both.” Fish appears to
`meet this limitation by its use of PLL. See, e.g., Ex. 1006, 539, Fig. 1 (“PLL
`treated microtitration wells were coated with various preparations of double-
`stranded and single-stranded DNA.”).
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that dependent claims 105, 106, 114, 116, 119, 128, 129, 150, 152, 178, 180,
`186, and 187—but not claim 131—are anticipated by Fish.
`
`16
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`IPR2016-00822
`Patent 7,064,197 B1
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`C. Ground 2: Obviousness in View of Fish
`
`Petitioner contends that dependent claims 130, 131, 151, and 154
`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 Co., 383
`U.S. 1, 17 (1966).13
`
`Claim 131 depends directly from independent claim 17 and adds that
`the fixed or immobilized “nucleic acids comprise nucleic acid sequences
`complementary to nucleic acid sequences 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 claim
`131.” Ex. 1002 ¶80; see also Pet. 33 (citing the same). We find this
`testimony persuasive.
`
`13 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.
`
`17
`
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`IPR2016-00822
`Patent 7,064,197 B1
`
`Claim 130 depends directly from independent claim 17 and adds that
`the “nucleic acids [are] RNA.” Similarly, claim 154 depends directly from
`independent claim 25 and adds that the “nucleic acids are RNA.” Claim 151
`depends directly from independent claim 25 and adds that the “nucleic acids
`comprise a gene sequence or pathogen sequence.” 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. 33–34.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that dependent claims 130, 131, 151, and 154 would have been obvious over
`Fish.
`
`D. Ground 3: Obviousness in View of Fish, Metzgar and Sato
`
`Petitioner contends that dependent claims 120 and 189 would have
`been obvious over Fish, Metzgar, and Sato. Pet. 6. Claim 120 depends
`directly from independent claim 17, and claim 189 depends directly from
`independent claim 25. Claims 120 and 189 additionally recite that “said
`non-porous solid support comprises one or more hydroxyls.”
`
`Petitioner provides testimony from Dr. Nelson (Ex. 1002 ¶83) that
`glass necessarily includes hydroxyl groups and identifies teachings from
`Metzgar and Sato to show why it would have been obvious to use glass
`trays, instead of polyvinyl trays, in Fish. Pet. 35–36. In particular,
`Petitioner notes that Metzgar discloses microscope slides made of glass and
`having “depressions or wells on the top surface thereof” and that Sato
`discloses treatment of glass slides with PLL prior to fixing cells on the
`slides, thus indicating that PLL treatment of glass slides was a known and
`18
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`IPR2016-00822
`Patent 7,064,197 B1
`
`routine practice. Pet. 35 (quoting Ex. 1009, Abstract and citing Ex. 1009,
`2:28–30 and Fig. 1), 36 (citing Ex. 1034, 647 ¶4). In light of these
`teachings, Petitioner persuasively argues, that a person of ordinary skill in
`the art would have been motivated “to perform the nucleic acid
`immobilization procedure described in Fish [which uses PLL] on easy-to-
`use, non-porous supports, such as the glass slides having wells or
`depressions, as disclosed in Metzgar.” Pet. 35–36.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that dependent claims 120 and 189 would have been obvious over Fish,
`Metzgar, and Sato.
`
`E. Ground 4: Obviousness in View of Fish and Gilham
`
`Petitioner contends that dependent claims 113 and 185 would have
`been obvious over Fish and Gilham. Pet. 6. Claim 113 depends directly
`from independent claim 17, and claim 185 depends directly from
`independent claim 25. Claims 113 and 185 additionally recite that “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 ¶85 (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
`19
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`IPR2016-00822
`Patent 7,064,197 B1
`
`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. 38. We find this reasoning
`adequate.
`
`There is a reasonable likelihood Petitioner would prevail in showing
`that dependent claims 113 and 185 would have been obvious over Fish and
`Gilham.
`
`F. Ground 5: Obviousness in View of VPK and Metzgar
`
`Petitioner contends that claims 17, 19, 25, 105, 106, 114, 119, 120,
`128, 129, 131, 150–152, 178, 180, 186, and 189 would have been obvious
`over VPK and Metzgar. Pet. 6.
`
`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 challen
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