Trials@uspto.gov
`571-272-7822
`
`Paper 64
`Date: August 15, 2016
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_____________
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`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`____________
`
`ARIOSA DIAGNOSTICS
`Petitioner,
`
`v.
`
`VERINATA HEALTH, INC.
`Patent Owner.
`____________
`
`Cases IPR2013-00276 and IPR2013-00277
`Patent 8,318,430 B2
`____________
`
`
`Before TONI R. SCHEINER, LORA M. GREEN, and RAMA G. ELLURU,
`Administrative Patent Judges.
`
`GREEN, Administrative Patent Judge.
`
`
`
`DECISION ON REMAND
`35 U.S.C. § 144 and 37 C.F.R. § 42.5(a)
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`
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`

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`Cases IPR2013-00276 and IPR2013-00277
`Patent 8,318,430
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`BACKGROUND
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`
`
`
`
`In IPR2013-00276, Ariosa Diagnostics, Inc. (“Petitioner” or “Ariosa”)
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`filed a Petition requesting inter partes review of claims 1–18 of U.S. Patent
`
`No. 8,318,430 B2 (Ex. 1001, “the ’430 patent”) pursuant to 35 U.S.C.
`
`§§ 311–319. IPR2013-00276, Paper 1 (“’276 Pet.”). Verinata Health, Inc.,
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`(“Patent Owner” or “Verinata”) filed a Preliminary Response. IPR2013-
`
`00276, Paper 10 (“’276 Prelim. Resp.”). On the basis of the Petition and the
`
`Preliminary Response, we determined that Petitioner had demonstrated a
`
`reasonable likelihood of prevailing with respect to at least one of the
`
`challenged claims, and on October 25, 2013, an inter partes review of claims
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`1–18 was instituted on the asserted ground that the claims would have been
`
`unpatentable over the combined teachings of Shoemaker,1 Dhallan,2 and
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`Binladen.3 IPR2013-00276, Paper 11 (“’276 Dec.”), 21. After institution of
`
`trial, Patent Owner filed a Patent Owner Response (IPR2013-00276, Paper
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`20, “’276 PO Resp.”), to which Petitioner filed a Reply (IPR2013-00276,
`
`Paper 26, “’276 Reply”).
`
`In IPR2013-00277, Ariosa filed a Petition requesting inter partes
`
`review of claims 19–30 of the ’430 patent (Ex. 1001) pursuant to 35 U.S.C.
`
`§§ 311–319. IPR2013-00277, Paper 1 (“’277 Pet.”). Verinata filed a
`
`
`1 Shoemaker et al., Pub. No. US 2008/0090239 A1, published Apr. 17, 2008
`(“Shoemaker”) (Ex. 1008).
`
`2 Dhallan, Patent No. US 7,322,277 B2, issued Feb. 19, 2008 (“Dhallan”)
`(Ex. 1004).
`
`3 Jonas Binladen et al., The Use of Coded PCR Primers Enables
`High-Throughput Sequencing of Multiple Homolog
`Amplification Products by 454 Parallel Sequencing, 2 PLOS
`ONE 1–9 (2007) (“Binladen”) (Ex. 1005).
`
`2
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`Cases IPR2013-00276 and IPR2013-00277
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`Preliminary Response. IPR2013-00277, Paper 9 (“’277 Prelim. Resp.”). On
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`the basis of the Petition and the Preliminary Response, we determined that
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`Petitioner had demonstrated a reasonable likelihood of prevailing with
`
`respect to at least one of the challenged claims, and on October 25, 2013, an
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`inter partes review of claims 19–30 was instituted on the asserted ground
`
`that the claims would have been unpatentable over the combined teachings
`
`of Shoemaker, Dhallan, and Binladen. IPR2013-00277, Paper 10 (“’277
`
`Dec.”), 21. After institution of trial, Patent Owner filed a Patent Owner
`
`Response (IPR2013-00277, Paper 19, “’277 PO Resp.”), to which Petitioner
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`filed a Reply (IPR2013-00277, Paper 25, “’277 Reply”).
`
`
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`Oral argument was requested by both parties in both proceedings, and
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`a consolidated argument was held on July 16, 2014. A transcript of the oral
`
`hearing is in the record. Paper 42,4 “Tr.”
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`
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`On October 23, 2014, we issued Final Written Decisions in both
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`proceedings in accordance with 37 C.F.R. § 42.73. We concluded that
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`Petitioner had failed to demonstrate by a preponderance of the evidence that
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`claims 1–30 are unpatentable. IPR2013-00276, Paper 43 (“’276 Final
`
`Written Decision”), 23 (challenged claims 1–18); IPR2013-00277, Paper 42,
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`(“’277 Final Written Decision”), 23 (challenged claims 19–30). Petitioner
`
`appealed the ’276 Final Written Decision and the ’277 Final Written
`
`Decision to the United States Court of Appeals for the Federal Circuit.
`
`
`
`The Federal Circuit consolidated the appeals of the two inter partes
`
`review proceedings, and issued a decision on November 16, 2015. Ariosa
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`Diagnostics v. Verinata Health, Inc., 805 F.3d 1359 (Fed. Cir. 2015). In
`
`
`4 If a particular proceeding is not referenced, all paper numbers refer to the
`paper numbers in IPR2013-00276.
`
`3
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`particular, the court noted that we may have erred by not considering Exhibit
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`1010, an Illumina Brochure, “even as evidence of the background
`
`understanding of skilled artisans as of January 2010, simply because the
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`brochure had not been identified at the petition stage as one of the pieces of
`
`prior art defining a combination for obviousness.” Id. at 1365. The court,
`
`therefore, vacated our finding of nonobviousness and remanded the case.
`
`The Federal Circuit’s mandate issued on December 23, 2015.
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`
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`A conference call was held on January 8, 2016, to discuss the
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`procedure to be taken post-remand. We authorized Petitioner to file a
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`fifteen-page brief, “limited to how we may have overlooked how Petitioner
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`relied upon Exhibit 1010 in the record that went up to the Court of Appeals
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`for the Federal Circuit on appeal.” Paper 49, 3. We noted that we would not
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`consider any argument or evidence that was not before the Federal Circuit
`
`on appeal. Id. at 4. We authorized Patent Owner to file a fifteen-page
`
`opposition. Id. We also authorized Petitioner authorization to file a five-
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`page Reply.
`
`In accordance with the Board’s Order, Petitioner filed its Opening
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`Brief on Remand on January 22, 2016. Paper 53. Patent Owner filed a
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`Remand Opposition Brief on February 5, 2016 (Paper 56), and Petitioner
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`filed its Reply Brief on Remand on February 24, 2016 (Paper 60).
`
`On remand, Petitioner argues “(1) that the proper context for
`
`consideration of Ex. 1010 is the combination of references on which review
`
`was instituted, which utilized Shoemaker (not Dhallan) as the primary
`
`reference; (2) that the Petition and supporting declarations properly
`
`presented Ex. 1010 as evidence of the state of the art in which a skilled
`
`artisan would view the combination of the art of the instituted ground; and
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`(3) that when properly considered, this evidence demonstrates that the
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`
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`asserted claims are obvious.” Paper 53, 1.
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`The Board has reviewed the record in light of the Federal Circuit’s
`
`decision and the arguments of the parties. For the reasons that follow, we
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`again conclude that Petitioner has not demonstrated by a preponderance of
`
`the evidence that the combination of Shoemaker, Dhallan, and Binladen
`
`renders challenged claims 1–30 of the ʼ430 patent unpatentable under
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`35 U.S.C. § 103(a).
`
`ANALYSIS
`
`A. The ’430 Patent
`
`The ’430 patent discloses a method for determining the presence or
`
`absence of fetal aneuploidy—a condition in which a fetus carries an
`
`abnormal number of chromosomes—by determining the relative amounts of
`
`non-random polynucleotide sequences from a chromosome suspected of
`
`being aneuploid, and from a reference chromosome or a chromosome
`
`control region, in a cell-free sample from a pregnant woman. Ex. 1001,
`
`1:23–27, 2:10–11, 13:9–12, 19:18–19. The ’430 patent further discloses
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`determining simultaneously the presence or absence of fetal aneuploidy in
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`pooled, indexed, cell-free samples from a plurality of pregnant women,
`
`using massively parallel sequencing. Id. at 1:23–25, 1:66–67.
`
`Briefly, cell-free samples (e.g., maternal serum or plasma) containing
`
`both maternal and fetal nucleic acid fragments are obtained from a plurality
`
`of pregnant women. Id. at 1:41–44. In each sample, non-random
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`polynucleotide sequences from a chromosome suspected of being aneuploid,
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`and non-random sequences from a reference chromosome or chromosome
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`control region, are enriched selectively and indexed (i.e., tagged for later
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`identification as originating from a particular sample). Id. at 22:9–15. The
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`
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`enriched, indexed samples are pooled, and the enriched, indexed nucleic
`
`acids are sequenced by massively parallel sequencing to produce sequence
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`reads. Id. The number of sequence reads from the chromosome suspected
`
`of being aneuploid, and the number of sequence reads from the reference
`
`chromosome or a chromosome control region, are counted, and the two
`
`numbers are compared to determine whether there is an abnormal level of
`
`DNA associated with the chromosome suspected of being aneuploid. Id. at
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`1:45–48, 17:53–59. As discussed above, indexing allows results from
`
`different samples to be distinguished. Ex. 1001, 22:10–15.
`
`B. Illustrative Claims
`
`Of challenged claims 1–30, claims 1 and 19 are independent, are
`
`illustrative of the claimed subject matter, and are reproduced below:
`
`1. A method for determining a presence or absence of a fetal
`aneuploidy in a fetus for each of a plurality of maternal blood
`samples obtained from a plurality of different pregnant women,
`said maternal blood samples comprising fetal and maternal cell-
`free genomic DNA, said method comprising:
`
`(a) obtaining a fetal and maternal cell-free genomic DNA sample
`from each of the plurality of maternal blood samples;
`
`a plurality of non-random
`enriching
`selectively
`(b)
`polynucleotide sequences of each fetal and maternal cell-free
`genomic DNA sample of (a) to generate a library derived from
`each fetal and maternal cell-free genomic DNA sample of
`enriched and
`indexed
`fetal and maternal non-random
`polynucleotide sequences, wherein each library of enriched and
`indexed
`fetal and maternal non-random polynucleotide
`sequences includes an indexing nucleotide sequence which
`identifies a maternal blood sample of the plurality of maternal
`blood samples, wherein said plurality of non-random
`polynucleotide sequences comprises at least 100 different non-
`random polynucleotide sequences selected from a first
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`chromosome tested for being aneuploid and at least 100 different
`non-random polynucleotide sequences selected from a reference
`chromosome, wherein the first chromosome tested for being
`aneuploid and the reference chromosome are different, and
`wherein each of said plurality of non-random polynucleotide
`sequences is from 10 to 1000 nucleotide bases in length,
`
`(c) pooling the libraries generated in (b) to produce a pool of
`enriched and
`indexed
`fetal and maternal non-random
`polynucleotide sequences;
`
`(d) performing massively parallel sequencing of the pool of
`enriched and
`indexed
`fetal and maternal non-random
`polynucleotide sequences of (c) to produce sequence reads
`corresponding to enriched and indexed fetal and maternal non-
`random polynucleotide sequences of each of the at least 100
`different non-random polynucleotide sequences selected from
`the first chromosome tested for being aneuploid and sequence
`reads corresponding to enriched and indexed fetal and maternal
`non-random polynucleotide sequences of each of the at least 100
`different non-random polynucleotide sequences selected from
`the reference chromosome;
`
`(e) based on the indexing nucleotide sequence, for each of the
`plurality of maternal blood samples, enumerating sequence reads
`corresponding to enriched and indexed fetal and maternal non-
`random polynucleotide sequences selected from the first
`chromosome tested for being aneuploid and sequence reads
`corresponding to enriched and indexed fetal and maternal non-
`random polynucleotide sequences selected from the reference
`chromosome; and
`
`(f) for each of the plurality of maternal blood samples,
`determining the presence or absence of a fetal aneuploidy
`comprising using a number of enumerated sequence reads
`corresponding to the first chromosome and a number of
`enumerated sequence reads corresponding to the reference
`chromosome of (e).
`
`
`
`19. A method for determining a presence or absence of a fetal
`aneuploidy in a fetus for each of a plurality of maternal blood
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`samples obtained from a plurality of different pregnant women,
`said maternal blood samples comprising fetal and maternal cell-
`free genomic DNA, said method comprising:
`
`(a) obtaining a fetal and maternal cell-free genomic DNA sample
`from each of the plurality of maternal blood samples;
`
`a plurality of non-random
`enriching
`selectively
`(b)
`polynucleotide sequences of each fetal and maternal cell-free
`genomic DNA sample of (a) to generate a library derived from
`each fetal and maternal cell-free genomic DNA sample of
`enriched and
`indexed
`fetal and maternal non-random
`polynucleotide sequences, wherein each library of enriched and
`indexed
`fetal and maternal non-random polynucleotide
`sequences includes an indexing nucleotide sequence which
`identifies a maternal blood sample of the plurality of maternal
`blood samples, wherein said plurality of non-random
`polynucleotide sequences comprises at least 100 different non-
`random polynucleotide sequences selected from at least one
`chromosome region tested for being aneuploid and at least 100
`different non-random polynucleotide sequences selected from at
`least one chromosome control region, wherein the at least one
`chromosome region tested for being aneuploid and the at least
`one chromosome control region are different, and wherein each
`of said plurality of non-random polynucleotide sequences is from
`10 to 1000 nucleotide bases in length,
`
`(c) pooling the libraries generated in (b) to produce a pool of
`enriched and
`indexed
`fetal and maternal non-random
`polynucleotide sequences;
`
`(d) performing massively parallel sequencing of the pool of
`enriched and
`indexed
`fetal and maternal non-random
`polynucleotide sequences of (c) to produce sequence reads
`corresponding to enriched and indexed fetal and maternal non-
`random polynucleotide sequences of each of the at least 100
`different non-random polynucleotide sequences selected from
`the at least one chromosome region tested for being aneuploid
`and sequence reads corresponding to enriched and indexed fetal
`and maternal non-random polynucleotide sequences of each of
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`the at least 100 different non-random polynucleotide sequences
`selected from the at least one chromosome control region;
`
`(e) based on the indexing nucleotide sequence, for each of the
`plurality of maternal blood samples, enumerating sequence reads
`corresponding to enriched and indexed fetal and maternal non-
`random polynucleotide sequences selected from the at least one
`chromosome region tested for being aneuploid and sequence
`reads corresponding to enriched and indexed fetal and maternal
`non-random polynucleotide sequences selected from the at least
`one chromosome control region; and
`
`(f) for each of the plurality of maternal blood samples,
`determining the presence or absence of a fetal aneuploidy
`comprising using a number of enumerated sequence reads
`corresponding to the at least one chromosome region tested for
`being aneuploid and a number of enumerated sequence reads
`corresponding to the at least one chromosome control region of
`(e).
`
`C. The Final Written Decisions
`
`In both the ’276 Final Written Decision and the ’277 Final Written
`
`Decision, we reviewed the teachings of Shoemaker, Dhallan, and Binladen.
`
`’276 Final Written Decision, 8–10; ’277 Final Written Decision, 8–10.
`
`After summarizing the teachings of those references, we noted that upon
`
`consideration of the Petition, as well as the Declarations of Drs. Morton and
`
`Nussbaum, Petitioner had failed to demonstrate the unpatentability of the
`
`challenged claims by a preponderance of the evidence. ’276 Final Decision,
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`16; ’277 Final Written Decision, 16. In particular, we noted that “[a]lthough
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`the Petition and accompanying Declarations point to disparate elements of
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`the three references, and attempt to map them to elements of the challenged
`
`claims, virtually no effort is made to explain how or where the references
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`differ from the challenged claims, how one of ordinary skill in the art would
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`go about combining their disparate elements, or what modifications one of
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`ordinary skill in the art would necessarily have made in order to combine the
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`disparate elements.” ’276 Final Decision, 16.5 We concluded, therefore,
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`that the Petition and accompanying Declarations failed to provide “an
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`‘articulated reason[] with some rational underpinning to support the legal
`
`conclusion of obviousness.’” Id. (quoting In re Kahn, 441 F.3d 977, 988
`
`(Fed. Cir. 2006)).
`
`
`
`As to Exhibit 1010, we noted that we were not “persuaded by the
`
`belated attempt in the Reply and Dr. Morton’s Second Declaration to bolster
`
`Petitioner’s initial obviousness challenge by reference to technical advances,
`
`e.g., massively parallel sequencing (“MPS”), that one of ordinary skill in the
`
`art would have been aware of ‘in the years between the filing of Dhallan and
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`the earliest claimed priority date.’” Id. at 17. In particular, we noted that the
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`testimony of Dr. Morton in her Second Declaration (Ex. 1042 ¶¶ 42–43), “in
`
`effect, replaces the tagging and sequencing techniques of Dhallan and
`
`Binladen with the Illumina indexing kit and sequencing platform, but neither
`
`Petitioner nor Dr. Morton explains why Exhibit 1010 could not have been
`
`presented as part of the asserted ground of unpatentability in the first
`
`instance with the Petition.” Id. at 19. We, thus, exercised our discretion to
`
`accord that aspect of the testimony of Dr. Morton little weight. Id.
`
`
`5 We determine there is no need to cite to the papers and exhibits in both
`proceedings given the identity of the issues in both proceedings addressed
`here. See, e.g., Ariosa, 805 F.3d at 1360 n.1 (noting the “board’s decisions
`are the same in all respects material to this opinion. Instead of providing
`duplicative citations, we cite only the decision in IPR2013-00276, which we
`call simply ‘Ariosa.’”).
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`D. The Decision of the Federal Circuit
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`
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`On appeal to the Federal Circuit, Petitioner argued that we “erred in
`
`refusing to consider Exhibit 1010 for what it showed about the background
`
`knowledge that a skilled artisan would have possessed, particularly about
`
`DNA indexing, in January 2010.” Ariosa, 805 F.3d at 1365. The Federal
`
`Circuit noted that our language in the Final Written Decision, “on its face,”
`
`supported Petitioner’s assertion that we declined to consider Exhibit 1010 as
`
`evidence of what the understanding of the ordinary artisan would have been
`
`at the relevant time period “simply because the brochure had not been
`
`identified at the petition stage as one of the pieces of prior art defining a
`
`combination for obviousness.” Id. According to the Federal Circuit, if that
`
`was what we in fact meant to say, we erred, as “[a]rt can legitimately serve
`
`to document the knowledge that skilled artisans would bring to bear in
`
`reading the prior art identified as producing obviousness.” Id. (citing
`
`Randall Mfg. v. Rea, 733 F.3d 1355, 1362–63 (Fed. Cir. 2013)). The
`
`Federal Circuit stated that Petitioner was in fact using Exhibit 1010 in that
`
`manner. Id.
`
`The Federal Circuit noted, however, that it was unclear whether we
`
`declined to give much weight to Exhibit 1010 on a legally proper ground.
`
`Id. at 1366. Specifically, according to the Federal Circuit:
`
`The Board might have been saying only that the development of
`the argument invoking Exhibit 1010 in the Petitions was not
`adequate. This court in Randall did not dispense with the need
`for parties to provide adequately developed explanations when
`relying on background knowledge based on cited art; the
`adequacy of the challenger’s explanation in that regard was
`unquestioned in Randall. 733 F.3d at 1360. And a PTO
`regulation provides: “[t]he Board may exclude or give no weight
`to the evidence where a party has failed to state its relevance.”
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`37 C.F.R. § 42.104(b)(5). In the present case, other than stating
`that massively parallel sequencing was known by 2008, the
`Petitions and supporting declarations say little about the
`relevance of Exhibit 1010, such as how a skilled artisan would
`have used what it showed about background knowledge in
`combining or modifying the prior-art references or how it tended
`to show that a skilled artisan would have had a reasonable
`expectation of success in achieving the suggested combination
`and modification.
`
`Id.
`
`
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`As the Federal Circuit could not discern whether we had given Exhibit
`
`1010 little weight for a legally proper reason, or on an erroneous legal
`
`reason, it vacated and remanded the Final Written Decisions. Id. at 1366–
`
`68. In doing so, the Federal Circuit stated that it was unwilling to draw its
`
`own conclusions about whether Exhibit 1010 would have filled the
`
`“explanatory gap” of Petitioner’s obviousness challenge, given the
`
`complexity of the subject matter. Id.
`
`
`
`Petitioner argued also on appeal that we erred in failing to consider
`
`certain embodiments of Dhallan that do not require a restriction-enzyme
`
`digestible primer. Id. at 1367. The Federal Circuit noted that it saw “no
`
`error in the Board’s rejection of Ariosa’s reliance, in its Reply submissions,
`
`on previously unidentified portions of a prior-art reference to make a
`
`meaningfully distinct contention.” Id. Specifically, the Federal Circuit
`
`acknowledged that “[n]ot until Dr. Morton’s Reply declaration did Ariosa
`
`identify specific embodiments of Dhallan that do not use restriction-enzyme
`
`digestible primers.” Id. Thus, the Federal Circuit concluded that we did not
`
`err in determining that those portions of Dhallan that do not require a
`
`restriction-enzyme digestible primer were identified for the first time by
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`Ariosa in its Reply, and that we did not err in declining to rely upon those
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`embodiments in the obviousness analysis. Id. at 1368.
`
`
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`Finally, Petitioner also argued on appeal that we erred in not
`
`sufficiently considering the teachings of Shoemaker in the obviousness
`
`analysis. Id. The Federal Circuit noted in response that we had addressed
`
`Shoemaker throughout our analysis, but as the case was being remanded,
`
`remarked that we “may decide whether its treatment of Shoemaker should be
`
`left as is, supplemented, or revised.” Id.
`
`E. Patentability of Claims
`
`On remand, Petitioner argues that the “level of skill in the art, as
`
`evidenced by Ex. 1010, would be brought to bear in the context of the
`
`combination of Shoemaker, Dhallan and Binladen.” Paper 53, 5. That
`
`combination, Petitioner asserts, starts with the MPS detection of Shoemaker,
`
`which is performed on the Illumina Genome analyzer, to determine fetal
`
`aneuploidy, and thus, modifies the method of incorporating multiplexing as
`
`taught by Binladen. Id.
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`
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`Petitioner contends that there were two challenges presented in the
`
`Petition, and the one on which trial was instituted was based on the
`
`aneuploidy detection technique of Shoemaker, not Dhallan. Id. That
`
`challenge, Petitioner contends, “involves modification of Shoemaker’s
`
`detection method to use cell-free DNA as taught in Dhallan and indexing of
`
`individual samples as exemplified by Binladen.” Id. at 6. As set forth in the
`
`claim chart in the Petition, “the massively parallel sequencing method relied
`
`upon in the instituted combination is MPS on the Illumina Genome Analyzer
`
`as discussed in Shoemaker.” Id. (quoting ’276 Pet. 46 (discussing element
`
`(d) of claim 1)). That was recognized, Petitioner asserts, in the Decision on
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`Institution. Id. at 7 (quoting ’276 Dec. 18). Petitioner contends further that
`
`
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`the Federal Circuit recognized that distinction when it “noted that the
`
`Petitions presented multiple combinations based on Dhallan and that the
`
`second of those combinations relied on Dhallan only for the use of cell-free
`
`DNA.” Id. at 8 (citing Ex. 1050,6 8; Ariosa, 805 F.3d at 1363).
`
`
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`Moreover, Petitioner contends, the “petition and accompanying
`
`declarations properly referenced Ex. 1010 as evidence of the level of skill in
`
`the art.” Paper 53, 8 (citing ’276 Pet. 41–48; Ex. 1003 ¶¶ 19–23). Petitioner
`
`argues further that the Federal Circuit also recognized that the Illumina
`
`Brochure (Ex. 1010), could be used as evidence of the level of skill in the
`
`art. Id. at 9 (quoting Ex. 1050, 11–12; Ariosa, 805 F.3d at 1365). Petitioner
`
`asserts, the “Federal Circuit decision thus recognizes that the Petition
`
`presented the Illumina multiplexing kit as evidence that indexing (i.e.,
`
`multiplexing) could have been executed on the Illumina Genome Analyzer
`
`with a commercially-available kit.” Id. at 9–10.
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`
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`According to Petitioner, Patent Owner, in its Response, “constructed a
`
`straw man by advancing as its primary argument that Binladen’s tagging or
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`indexing method could not be combined with Dhallan’s sequencing
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`methods.” Id. at 10 (citing ’276 PO Resp. 50–52). That argument,
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`Petitioner argues, “has nothing to do with the sequencing technique used in
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`the ground on which trial was actually instituted, i.e., Shoemaker’s MPS
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`sequencing method performed on the Illumina Genome Analyzer.” Id.
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`Petitioner argues that we were apparently misled by that argument, as the
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`Final Written Decision “says nothing about whether a skilled artisan would
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`6 Exhibit 1050 is the slip opinion of the Federal Circuit’s decision in Ariosa.
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`have had difficulty performing indexing on the Illumina Genome Analyzer
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`used in Shoemaker,” but instead focuses on “the compatibility of Binladen’s
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`indexing technique with Dhallan’s detection technique involving restriction
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`digestible enzymes.” Id. (citing ’276 Final Written Decision 12–17).
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`According to Petitioner, that incompatibility is “irrelevant as it does not
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`address the combination on which trial was instituted.” Id.
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`Thus, Petitioner contends, “[u]nder a proper assessment of Petitioner’s
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`argument, including a skilled artisan’s knowledge of the commercial
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`availability of multiplexing kits as shown in Ex. 1010, Petitioner has
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`established that the challenged claims are obvious.” Id. at 11. Petitioner
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`argues that as explained in the Petition, “a skilled artisan would have
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`considered it obvious to modify Shoemaker’s MPS (performed on the
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`Illumina Genome Analyzer) to use cell-free DNA (taught by Dhallan) and
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`multiplexing (taught by Binladen).” Id. (citing Pet. 41). The Illumina
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`Brochure, Ex. 1010, demonstrates that the ordinary artisan “could perform
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`multiplexing on the Illumina Genome Analyzer by ordering a kit from
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`Illumina.” Id. (citing Pet. 11; Ex. 1003 ¶¶ 21–23).
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`Of note, Petitioner asserts, Patent Owner and its declarants “did not
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`argue that there was anything difficult about modifying MPS to include
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`indexing at the time of filing.” Id. at 13. Rather, Patent Owner argued “that
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`‘neither the petition nor the declarations of Ariosa’s experts provide
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`explanation of how the references could be modified or combined to arrive
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`at the ’430 patent claimed methods.’” Id. (citing PO Resp. 13). However,
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`according to Petitioner, “one skilled in the art would not attempt to bodily
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`incorporate Binladen’s specific indexes into the Illumina Genome Analyzer,
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`especially when an off-the-shelf multiplexing kit was available from
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`Illumina.” Id. at 14 (citing KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 421
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`(2007) for the proposition that “a person of ordinary skill has common sense
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`and is not a mere automaton”). Petitioner contends “[t]he Nussbaum
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`declaration [Ex. 1003] and Ex. 1010 clearly and indisputably showed that
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`Shoemaker’s MPS technique could have been modified with ease to include
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`the indexing suggested by Binladen. Indeed, from a technical perspective
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`nothing could be easier than ordering an off-the-shelf kit.” Id. at 14–15.
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`Patent Owner responds:
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`Although Ariosa successfully caused the Federal Circuit to
`accept the possibility that the Board might not have properly
`considered Exhibit 1010, the Federal Circuit nevertheless
`recognized that the Board may simply have found that “the
`development of the argument invoking Exhibit 1010 in the
`Petitions was not adequate.” The Federal Circuit explained that
`this “inadequate-explanation” reading of the Board’s original
`decision is consistent with the Board’s fundamental finding that
`Ariosa broadly failed to develop its obviousness theory and that,
`even in her reply declaration, Dr. Morton did not adequately
`address how Exhibit 1010 would have supported Ariosa’s
`obviousness theory.
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`Paper 56, 2 (citations omitted). Patent Owner asserts, therefore, that we
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`“properly considered Exhibit 1010.” Id.
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`
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`We conclude that we did not improperly fail to consider the Illumina
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`Brochure (Ex. 1010) as evidence of the level of skill in the art. Instead,
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`when the challenge over Shoemaker, Dhallan, and Binladen as presented in
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`the Petitions is considered in view of the Illumina Brochure, the Petitions
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`fail to demonstrate the unpatentability of the challenged claims by a
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`preponderance of the evidence for the reasons set forth in the Final Written
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`Decisions.
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`As to the challenge over Shoemaker, Dhallan, and Binladen, the
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`Petition states:
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`A scientist in this field would have known that Dhallan could be
`enhanced through use of the PCR amplification techniques
`utilizing sample indices and massively parallel sequencing of
`pooled samples as discussed in Binladen. Professors Nussbaum
`and Morton explain in their declarations that a skilled artisan
`would also have readily understood that Shoemaker’s methods
`for determining the presence of fetal abnormalities could be
`carried out with the use of cell-free DNA described in Dhallan
`and the multiplexed detection techniques taught in Binladen.
`(Nussbaum Declaration ¶¶ 109-165; Morton Declaration ¶¶98-
`129)
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`’276 Pet. 40–41.
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`
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`Petitioner, however, provided no further explanation of the
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`combination in the Petition, such as a reason with rational underpinning as to
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`why the ordinary artisan would have combined the references to arrive at the
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`method of the challenged claims, but only presented a claim chart
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`demonstrating where the limitations of each challenged claim could be
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`found in the cited prior art.
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`As noted by the Final Written Decision (’276 Final Written Decision
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`11), we acknowledged that Dr. Morton testified:
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`[A] skilled artisan would read Dhallan in the context of the state
`of the art in indexed PCR amplification techniques as discussed
`in Binladen. A skilled artisan reading Shoemaker would
`understand that the disclosed methods for determining the
`presence of fetal abnormalities could be carried out with the
`Dhallan/Binladen techniques. It is my view that the state of the
`art as reflected by Shoemaker, Dhallan and Binladen makes
`obvious the techniques described in claims 1–18 of the ’430
`patent.
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`Ex. 1002 ¶ 98.
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`We also acknowledged (’276 Final Written Decision 11) the
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`following testimony of Dr. Nussbaum:
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`[T]his combination discloses each element of Claims 1–18 of the
`’430 patent and [I] believe that one skilled in the art would have
`been motivated to combine these techniques, as the combination
`would clearly result in an enhanced productivity and increased
`throughput of sample analysis. The sequencing and multiplexing
`technology of Binladen would have made the procedures of
`Shoemaker and Dhallan less expensive, faster and more efficient
`bec