Case: 15-1215 Document: 54-2 Page: 1 Filed: 11/16/2015
`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`ARIOSA DIAGNOSTICS,
`Appellant
`
`v.
`
`VERINATA HEALTH, INC.,
`Appellee
`______________________
`
`2015-1215, 2015-1226
`______________________
`
`Appeals from the United States Patent and Trade-
`mark Office, Patent Trial and Appeal Board in Nos.
`IPR2013-00276, IPR2013-00277.
`______________________
`
`Decided: November 16, 2015
`______________________
`
`
`MARK A. LEMLEY, Durie Tangri LLP, San Francisco,
`CA, argued for appellant. Also represented by DARALYN
`JEANNINE DURIE, ALEXANDRA HELEN MOSS; GREG
`GARDELLA, Oblon, Spivak, McClelland, Maier & Neustadt,
`LLP, Alexandria VA.
`
`EDWARD R. REINES, Weil, Gotshal & Manges LLP,
`Redwood Shores, CA, argued for appellee. Also represent-
`ed by DEREK C. WALTER, ANANT N. PRADHAN; MICHAEL T.
`ROSATO, Wilson, Sonsini, Goodrich & Rosati, PC, Seattle,
`WA.
`
`______________________
`
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 1
`
`

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`Case: 15-1215 Document: 54-2 Page: 2 Filed: 11/16/2015
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`Before PROST, Chief Judge, WALLACH, and TARANTO,
`Circuit Judges.
`TARANTO, Circuit Judge.
`Verinata Health, Inc. owns U.S. Patent No. 8,318,430,
`which describes and claims methods of noninvasive pre-
`natal testing for the presence of fetal chromosomal ab-
`normalities. In particular, the methods may identify
`“aneuploidy,” i.e., the presence of an abnormal number of
`copies of a chromosome—say, three rather than the
`normal two for chromosome 21, an abnormality that
`characterizes Down Syndrome. The methods involve
`obtaining blood samples from several pregnant women;
`isolating from the samples genomic DNA molecules not
`contained in cells; choosing particular DNA sequences—
`some on a chromosome of concern, some not; indexing by
`maternal source the chromosomes or regions containing
`those sequences; amplifying (making many copies of) the
`group of chromosomes or regions; performing massively
`parallel sequencing on the resulting pool; using the index-
`ing to count, for a particular maternal source, the number
`of sequences from chromosomes of concern versus the
`number from reference chromosomes or regions; and
`determining based on the comparison whether there are
`fetal chromosomal abnormalities, such as an extra copy of
`a chromosome of concern.
`Ariosa Diagnostics, Inc. petitioned the Patent Trial
`and Appeal Board for inter partes review of claims 1–18
`and, in a separate petition, claims 19–30, challenging the
`claims for obviousness under 35 U.S.C. § 103. The Board
`concluded that Ariosa had not met its burden of proving
`that claims 1–18 and 19–30 would have been obvious.
`Ariosa Diagnostics v. Verinata Health, Inc., IPR2013-276,
`2014 WL 5454541 (PTAB Oct. 23, 2014); Ariosa Diagnos-
`tics v. Verinata Health, Inc., IPR2013-277, 2014 WL
`5454542 (PTAB Oct. 23, 2014). We vacate the decisions
`and remand for further consideration because of one
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 2
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`Case: 15-1215 Document: 54-2 Page: 3 Filed: 11/16/2015
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`matter that the Board’s language suggests it did not
`sufficiently consider.1
`
`BACKGROUND
`Verinata and Ariosa are competitors in the relatively
`new field of noninvasive prenatal diagnostics, which
`includes testing for fetal chromosomal abnormalities. For
`many years, prenatal chromosomal testing required
`invasive, high-risk procedures, such as amniocentesis.
`Noninvasive tests, based on the combination of ultra-
`sound observation and measurement of biochemical
`markers in blood samples drawn from the pregnant
`woman, suffered from low accuracy—in a matter where
`accuracy is very important. The 1997 discovery of cell-
`free fetal DNA circulating in maternal blood suggested
`the possibility of superior noninvasive tests, but turning
`the possibility into a reality presented significant chal-
`lenges.
`One challenge involved the proportion of the total
`amount of cell-free DNA in maternal blood that came
`from the fetus. That proportion is typically less than 10
`percent. Some scientists seeking to use the 1997 discov-
`ery focused on distinguishing fetal DNA from maternal
`DNA in a blood sample. By separating fetal from mater-
`nal DNA, or determining the particular fetal/maternal
`ratio of cell-free DNA, certain counting methods could try
`to discern which fetus-specific chromosomes had an
`abnormal number of copies.
`Verinata’s ’430 patent, with a priority date of January
`2010, does not rely on separating fetal from maternal cell-
`free DNA or, even, determining the fetal/maternal ratio of
`cell-free DNA. ’430 patent, col. 5, lines 63–65. Rather,
`
`1 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 IPR2013-276, which
`we call simply “Ariosa.”
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 3
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`Case: 15-1215 Document: 54-2 Page: 4 Filed: 11/16/2015
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`the ’430 patent describes a counting technique applied to
`an overall pool of DNA segments, selected for comparing a
`chromosome of concern (say, chromosome 21) with a
`reference chromosome (or chromosomal region), making
`the comparison by identifying the respective DNA se-
`quences. Fetal aneuploidy (in the case of, for example,
`three versus two copies of a chromosome) may be deter-
`mined by comparing the number of sequences generated
`from the chromosome of concern with the number of
`sequences generated from a reference chromosome—
`counting copies from all cell-free DNA, whether fetal or
`maternal. Id., col. 13, lines 59–64. But because cell-free
`fetal DNA is such a small proportion of total cell-free
`DNA, the elevation in the target-sequence count will be
`small in an overall sample; and for the numerical eleva-
`tion to be significant and sufficiently reliable for prenatal
`testing, a large sample must be created and sequenced.
`The ’430 patent describes doing so by amplifying the
`target and reference sequences, pooling samples from
`several women and indexing them for later identification,
`and using massively parallel sequencing. ’430 patent, col.
`1, lines 41–48; id., col. 6, lines 20–27; id., col. 12, lines 56–
`63.
`Claim 1 of the patent states:
`1. A method for determining a presence or ab-
`sence 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 ma-
`ternal blood samples comprising fetal and mater-
`nal
`cell-free genomic DNA,
`said method
`comprising:
`(a) obtaining a fetal and maternal cell-free ge-
`nomic DNA sample from each of the plurality
`of maternal blood samples;
`(b) selectively enriching a plurality of non-
`random polynucleotide sequences of each fetal
`and maternal cell-free genomic DNA sample
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 4
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`Case: 15-1215 Document: 54-2 Page: 5 Filed: 11/16/2015
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`of (a) to generate a library derived from each
`fetal and maternal cell-free genomic DNA
`sample of enriched and indexed fetal and ma-
`ternal non-random polynucleotide sequences,
`wherein each library of enriched and indexed
`fetal and maternal non-random polynucleo-
`tide sequences includes an indexing nucleo-
`tide sequence which identifies a maternal
`blood sample of the plurality of maternal
`blood samples,
`wherein said plurality of non-random polynu-
`cleotide sequences comprises at least 100 dif-
`ferent non-random polynucleotide sequences
`selected from a first chromosome tested for
`being aneuploid and at least 100 different
`non-random polynucleotide sequences select-
`ed 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 pro-
`duce a pool of enriched and indexed fetal and
`maternal non-random polynucleotide se-
`quences;
`(d) performing massively parallel sequencing of
`the pool of enriched and indexed fetal and
`maternal non-random polynucleotide se-
`quences of (c) to produce sequence reads cor-
`responding to enriched and indexed fetal and
`maternal non-random polynucleotide se-
`quences of each of the at least 100 different
`non-random polynucleotide sequences select-
`ed from the first chromosome tested for being
`aneuploid and sequence reads corresponding
`to enriched and indexed fetal and maternal
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 5
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`Case: 15-1215 Document: 54-2 Page: 6 Filed: 11/16/2015
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`non-random polynucleotide sequences of each
`of the at least 100 different non-random poly-
`nucleotide sequences selected from the refer-
`ence chromosome;
`(e) based on the indexing nucleotide sequence,
`for each of the plurality of maternal blood
`samples, enumerating sequence reads corre-
`sponding to enriched and indexed fetal and
`maternal non-random polynucleotide se-
`quences selected from the first chromosome
`tested for being aneuploid and sequence reads
`corresponding to enriched and indexed fetal
`and maternal non-random polynucleotide se-
`quences selected from the reference chromo-
`some; and
`(f) for each of the plurality of maternal blood
`samples, determining the presence or absence
`of a fetal aneuploidy comprising using a num-
`ber of enumerated sequence reads correspond-
`ing to the first chromosome and a number of
`enumerated sequence reads corresponding to
`the reference chromosome of (e).
`’430 patent, col. 63, lines 8–67. Claims 2–18 depend on
`claim 1 and add various limitations, such as the number
`of non-random DNA sequences selected, the length of the
`non-random DNA sequences, and the chromosomes to be
`tested. Id., col. 64, line 8 through col. 65, line 11. Claim
`19, the only other independent claim, differs from claim 1
`in that claim 19 requires comparing the tested chromo-
`some region to a chromosome control region, rather than
`comparing a tested chromosome to a reference chromo-
`some. Id., col. 65, lines 35–36, 55–56, 65, and col. 66, line
`7. Claims 20–30 depend on claim 19 and are largely
`analogous to claims 2–18. Id., col. 66, lines 1–62.
`Ariosa petitioned for inter partes review of claims 1–
`18 and 19–30. It argued that the claimed methods would
`have been obvious to a relevant skilled artisan in January
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 6
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`

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`Case: 15-1215 Document: 54-2 Page: 7 Filed: 11/16/2015
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`2010 in light of three prior-art references: Shoemaker,
`Dhallan, and Binladen.
`U.S. Patent Application No. 2008/0090239, filed in
`2008 by Shoemaker et al., discloses a method of determin-
`ing fetal aneuploidy by isolating fetal cells, not cell-free
`DNA. A maternal blood sample, known to include a very
`small number of fetal blood cells, is enriched for blood
`cells and then dispersed into wells, each well receiving at
`most one blood cell. Shoemaker ¶¶ 7, 8, 219. A polymer-
`ase chain reaction (PCR) technique is used to tag and
`amplify specific regions of chromosomes in those cells—
`regions being tested as well as control regions. Id. ¶¶ 7,
`9. All amplified products are then pooled for sequencing.
`Id. ¶ 121. Non-maternal sequences are identified and
`used to distinguish wells containing fetal cells from those
`containing maternal cells. Id. ¶ 138. For the wells that
`contain fetal cells, the ratio of maternal to non-maternal
`alleles is then compared: certain disparities will indicate
`the presence of extra copies of fetal chromosomes. Id.
`¶ 140.
`U.S. Patent No. 7,332,277, issued in 2003 to Dhallan,
`discloses a method of detecting fetal genetic disorders.
`Dhallan describes using a maternal blood sample to
`obtain a mixture of cell-free fetal and maternal DNA.
`’277 patent, col. 31, lines 32–34. Specific DNA sequences
`are amplified and sequenced. Id., col. 47, lines 38–39.
`After sequencing, maternal and fetal alleles are distin-
`guished, id., col. 67, lines 28–34, the percentage of fetal
`DNA in the original sample is calculated, id., col. 67, lines
`18–27, and the calculated ratio of fetal to maternal alleles
`is used to identify chromosomal abnormalities, id., col. 68,
`lines 56–60.
`An article published in 2007 by Jonas Binladen et al.
`describes a study that involved tagging and sequencing
`DNA samples from multiple sources simultaneously. The
`study isolated DNA samples from thirteen species (hu-
`man, wolf, cheetah, lion, hippopotamus, zebra, mouse,
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 7
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`Case: 15-1215 Document: 54-2 Page: 8 Filed: 11/16/2015
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`etc.) using a commercially available extraction kit, then
`amplified and indexed targeted sequences from those
`samples by methods of polymerase chain reaction that
`already were known. The amplified products were then
`pooled for sequencing, which was performed using a
`massively parallel sequencing machine.
`In its Petitions, Ariosa argued for obviousness based
`on combinations of Dhallan’s teachings about cell-free
`fetal DNA with Binladen’s indexing and sequencing
`techniques and Shoemaker’s method of determining
`aneuploidy. Specifically, Ariosa argued that “a scientist
`in this field would have known that Dhallan could be
`enhanced through use of the PCR amplification tech-
`niques utilizing sample indices and massively parallel
`sequencing of pooled samples as discussed in Binladen.”
`J.A. 208–09. It added “that a skilled artisan would have
`readily understood that Shoemaker’s methods for deter-
`mining the presence of fetal abnormalities could be car-
`ried out with the use of cell-free DNA described in
`Dhallan and the multiplexed detection techniques taught
`in Binladen.” J.A. 209.
`The Board instituted reviews under 35 U.S.C. § 314(a)
`upon finding a reasonable likelihood that the methods of
`the ’430 patent’s claims were unpatentable because they
`would have been obvious. But after receiving the Patent
`Owner’s Response and accompanying submissions, then
`Ariosa’s Reply and accompanying submissions, and then
`counsel’s oral arguments, the Board upheld all of the
`claims. The Board concluded that Ariosa did not carry its
`burden of showing that the claims would have been
`obvious. 35 U.S.C. § 316(e).
`The Board’s central point was that Ariosa’s Petitions
`were lacking because “virtually no effort [wa]s made to
`explain how or where the references differ from the chal-
`lenged claims, how one of ordinary skill in the art would
`go about combining their disparate elements, or what
`modifications one of ordinary skill in the art would neces-
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 8
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`

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`Case: 15-1215 Document: 54-2 Page: 9 Filed: 11/16/2015
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`sarily have made in order to combine the disparate ele-
`ments.” Ariosa, at *10. The Board discussed all three
`references—including, repeatedly, Shoemaker. Id. at *5,
`6, 7, 9, 10, 11. It pointed to concessions of Ariosa’s ex-
`perts, Drs. Morton and Nussbaum, made in depositions
`after the Institution Decisions, that various modifications
`would have to be made to combine Dhallan and Binladen,
`including “that one ‘would do a different process to incor-
`porate the tags’ . . . and Binladen’s ‘tagging would not be
`the way that that was done, because the method of insert-
`ing the tag, the way it’s done now was not known at that
`time.’ ” Id. at *9. The Board found unpersuasive Dr.
`Morton’s assertion that “ ‘one of ordinary skill . . . would
`be able to easily apply the teachings of Binladen to opti-
`mize the tags to decrease the error rate and increase the
`accuracy,’ ” given that Binladen’s tagging method dis-
`played a high error rate and detection of fetal aneuploidy
`requires “ ‘highly precise methods for quantification.’ ” Id.
`(citing Dr. Morton’s declarations). The Board further
`noted that Dr. Morton, in her deposition, “was unable to
`recall describing ‘a synthesis of how to put [Shoemaker,
`Dhallan, and Binladen] together’ anywhere in her Decla-
`ration.” Id.
`The Board summarized:
`What is lacking in the Petition and accompanying
`Declarations is an “articulated reason[ ] with some
`rational underpinning to support the legal conclu-
`sion of obviousness.” [In re] Kahn, 441 F.3d [977,
`988 (Fed. Cir. 2006)]. The inadequacy of the obvi-
`ousness analysis in the Petition and accompany-
`ing Declarations is readily apparent when the
`disparate elements of the references are scruti-
`nized closely, as in Patent Owner’s response, and
`we decline to search through the record and piece
`together those teachings that might support Peti-
`tioner’s position. Cf. DeSilva v. DiLeonardi, 181
`F.3d 865, 866–67 (Fed. Cir. 1999) (“A brief must
`make all arguments accessible to the judges, ra-
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 9
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`Case: 15-1215 Document: 54-2 Page: 10 Filed: 11/16/2015
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`ther than ask them to play archeologist with the
`record.”).
`Ariosa, at *10.
`At the end of its analysis, the Board addressed Ari-
`osa’s attempt, through a second declaration of Dr. Morton
`accompanying its Reply, to bolster the reliance placed in
`the Petitions on a brochure that describes indexing and
`massively parallel sequencing using the commercially
`available Illumina Genome Analyzer System (Exhibit
`1010). Id. at *10–11. The Board stated:
`This testimony, 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 un-
`patentability in the first instance with the Peti-
`tion.4 Therefore we accord this aspect of Dr.
`Morton’s testimony no weight.
`Id. at *11. In the footnote to that passage, the Board
`quoted the PTO regulation declaring that “[a] reply may
`only respond to arguments raised in the corresponding . . .
`patent owner response,” 37 C.F.R. § 42.23(b), and the
`related explanation that “[r]eply evidence . . . must be
`responsive and not merely new evidence that could have
`been presented earlier to support the movant’s motion,”
`Rules of Practice for Trials before the Patent Trial and
`Appeal Board, 77 Fed. Reg. 48,612, 48,620 (Aug. 14,
`2014). Ariosa, at *11 n.4.
`Ariosa appeals the Board’s determinations of nonobvi-
`ousness as to claims 1–18 and 19–30. The appeal is
`authorized by 35 U.S.C. § 319. This court has jurisdiction
`under 28 U.S.C. § 1295(a)(4)(A).
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 10
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`Case: 15-1215 Document: 54-2 Page: 11 Filed: 11/16/2015
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`DISCUSSION
`This court reviews the Board’s ultimate determina-
`tions of obviousness de novo. Randall Mfg. v. Rea, 733
`F.3d 1355, 1362 (Fed. Cir. 2013). It reviews for substan-
`tial evidence the underlying factual findings, which
`include findings as to the scope and content of the prior
`art, the differences between the prior art and the claimed
`invention, the level of ordinary skill in the art, the pres-
`ence or absence of a motivation to combine or modify with
`a reasonable expectation of success, and objective indicia
`of non-obviousness. See, e.g., id.; PAR Pharm., Inc. v.
`TWI Pharms., Inc., 773 F.3d 1186, 1196–97 (Fed. Cir.
`2014); Tri-Med, Inc. v. Stryker Corp., 608 F.3d 1333, 1341
`(Fed. Cir. 2010). A petitioner in an inter partes review
`has the burden of proving a claim’s invalidity by a pre-
`ponderance of the evidence. 35 U.S.C. § 316(e).
`A
`Ariosa’s principal challenge is to the Board’s treat-
`ment of Exhibit 1010, the Illumina brochure. Pointing to
`the Board’s language about Exhibit 1010, quoted supra,
`Ariosa argues that the Board 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. We
`agree with Ariosa up to a point: the Board’s language
`leaves open the distinct possibility that the Board incor-
`rectly limited its consideration of Exhibit 1010.
`The Board’s language on its face supports Ariosa’s in-
`terpretation of what the Board meant—that the Board
`was declining to consider Exhibit 1010, even as evidence
`of the background understanding of skilled artisans as of
`January 2010, 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. If that is
`what the Board meant, the Board erred. Art can legiti-
`mately serve to document the knowledge that skilled
`artisans would bring to bear in reading the prior art
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 11
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`Case: 15-1215 Document: 54-2 Page: 12 Filed: 11/16/2015
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`identified as producing obviousness. Randall, 733 F.3d at
`1362–63. Ariosa’s Petitions and opening declarations
`invoked Exhibit 1010 in that way.
`Ariosa included Exhibit 1010 in its Petitions as an ex-
`hibit to Dr. Nussbaum’s expert declaration. Dr. Nuss-
`baum, in discussing the state of the art of indexing and
`sequencing technology, stated that “as of 2008, indexed
`multiplexing was so widespread as a technique that the
`company Illumina, Inc. offered a commercially available
`kit for production and analysis of indexed libraries from
`different samples of origin,” and the indexed libraries
`could have been “analyzed on a commercially-available
`massively parallel sequencing platform sold by the same
`vendor.” J.A. 876. Ariosa’s second expert, Dr. Morton,
`also named the Illumina sequencing system when discuss-
`ing the state of the art of massively parallel sequencing,
`although she did not specifically refer to Exhibit 1010.
`The Petitions then cited portions of Dr. Nussbaum’s and
`Dr. Morton’s declarations for the same proposition—that
`“[m]assively parallel sequencing methods were in routine
`use by 2008.” J.A. 179. Given those references in the
`Petitions and supporting declarations, Exhibit 1010 had
`to be considered by the Board even though it was not one
`of the three pieces of prior art presented as the basis for
`obviousness.
`That the language of the Board regarding Exhibit
`1010 is readily susceptible of being read to rest on an
`incorrect legal proposition, by itself, does not require
`setting aside the Board’s decisions. We may affirm an
`agency ruling if we may reasonably discern that it fol-
`lowed a proper path, even if that path is less than perfect-
`ly clear. Bowman Transp., Inc. v. Arkansas-Best Freight
`System, Inc., 419 U.S. 281, 285–86 (1974). We also may
`affirm if an erroneous portion of an agency’s ruling is
`ultimately non-prejudicial, i.e., not material to the bot-
`tom-line result given other portions of the agency’s ruling.
`5 U.S.C. § 706; 28 U.S.C. § 2111; In re Chapman, 595 F.3d
`1330, 1338 (Fed. Cir. 2010); In re Watts, 354 F.3d 1362,
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 12
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`1369 (Fed. Cir. 2004). But we must not ourselves make
`factual and discretionary determinations that are for the
`agency to make. In re Lee, 277 F.3d 1338, 1342 (Fed. Cir.
`2002); ICC v. Bhd. of Locomotive Eng’rs, 482 U.S. 270, 283
`(1987); SEC v. Chenery Corp., 332 U.S. 194, 196–97
`(1947).
`Here, we cannot confidently discern whether the
`Board, in its consideration of Exhibit 1010, was actually
`relying on a legally proper ground rather than the errone-
`ous ground just noted. 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 par-
`ties 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.” 37 C.F.R. § 42.104(b)(5). In the present
`case, other than stating that massively parallel sequenc-
`ing 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 combi-
`nation and modification.
`Giving the inadequate-explanation reading to the
`Board’s statement about Exhibit 1010, though straining
`the words somewhat, would fit two related aspects of the
`Board’s decisions. First, the Board’s statement followed
`its quotation of Dr. Morton’s Reply declaration, which
`contains little if any more explanation of Exhibit 1010’s
`role than appeared in her original declaration: “[O]ne of
`ordinary skill in January 2010 would be motivated to
`index individual samples and pool them for sequencing to
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 13
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`Case: 15-1215 Document: 54-2 Page: 14 Filed: 11/16/2015
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`maximize sequencing capacity and to minimize sequenc-
`ing cost. For example, the Illumina, Inc. product flyer
`from 2008 states, ‘[h]arnessing this sequencing power in a
`multiplexed fashion increases experimental throughput
`while reducing time and cost.’ ” Ariosa, at *11 (quoting
`J.A. 1485). Thus, while Dr. Morton’s Reply declaration
`identifies Exhibit 1010 as evincing a motivation to “index
`individual samples and pool them for sequencing,” it does
`not address whether Exhibit 1010 would have motivated a
`skilled artisan to replace the quantification methods of
`Dhallan, see, e.g., ’277 patent, col. 63, line 55 through col.
`65, line 28, with the technique of massively parallel
`sequencing described by Binladen. Second, at the heart of
`the Board’s analysis in the rest of its decisions is its
`finding that Ariosa provided inadequate explanation: the
`Petitions did not “explain how or where the references
`differ from the challenged claims, how one of ordinary
`skill in the art would go about combining their disparate
`elements, or what modifications one of ordinary skill in
`the art would necessarily have made in order to combine
`the disparate elements.” Ariosa, at *10.
`Yet the Board did not sufficiently articulate the fore-
`going grounds for its rejection of Ariosa’s reliance on
`Exhibit 1010 or other grounds independent of the incor-
`rect ground suggested by the Board’s language. Perhaps
`the Board could have done so. But it did not, and we
`cannot do so for the Board where, as here, the matter is
`not purely legal.
`We likewise are not prepared to find that the error we
`cannot rule out was non-prejudicial. We will not here
`draw our own conclusion about whether Exhibit 1010, if
`considered for what the Petitions (and supporting declara-
`tions) adequately presented about it, could have filled the
`explanatory gap that was the heart of the Board’s reason
`for finding Ariosa’s case unproved. Given the complexity
`of this area, and how seemingly small differences might
`be significant, we will not undertake to determine wheth-
`er a proper assessment of Exhibit 1010 should lead to a
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 14
`
`

`
`Case: 15-1215 Document: 54-2 Page: 15 Filed: 11/16/2015
`
`reassessment of the explanatory gap. The Board is in a
`better position to do so. We will therefore vacate the
`decisions and remand.
`We do not direct the Board to take new evidence or,
`even, to accept new briefing. The Board may control its
`own proceedings, consistent with its governing statutes,
`regulations, and practice. 37 C.F.R. § 42.5(a). Those
`statutes, regulations, and practices embody expedition-
`and efficiency-based policies that the Board must consider
`in determining the scope of the remand proceedings.
`Congress generally directed that inter partes review
`proceedings be completed within one year of institution.
`35 U.S.C. § 316(a)(11). Reflecting that timing constraint,
`and the statutory goal of providing a relatively quick and
`low-cost alternative to litigation over validity, the PTO
`has established rules that, while necessarily respecting
`constitutional and statutory guarantees of procedural
`fairness, are designed generally to require that the par-
`ties make their cases in a very small number of filings—
`with the challenger obliged to make an adequate case in
`its Petition and the Reply limited to a true rebuttal role.
`37 C.F.R. §§ 42.104(b)(5), 42.23(b). Within this structure,
`even while providing for an estoppel effect on the chal-
`lenger, 35 U.S.C. § 315(e), Congress assigned to the
`challenger the burden of persuasion in the dispute, id.
`§ 316(e). That burden, together with the procedural rules
`impartially applied, means that, in some cases, a chal-
`lenge can fail even if different evidence and arguments
`might have led to success. We leave to the Board the
`determination of what remand proceedings are appropri-
`ate given the governing policies.
`B
`Ariosa also challenges the Board’s decision on a dis-
`tinct ground. The Board determined that teachings of
`Binladen and Dhallan could not be combined because
`“Binladen’s indexing (i.e., tagging) scheme could not be
`used with Dhallan’s restriction-digestible amplification
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 15
`
`

`
`Case: 15-1215 Document: 54-2 Page: 16 Filed: 11/16/2015
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`primers.” Ariosa, at *10. Ariosa argues that the Board
`erred in failing to consider some embodiments of Dhal-
`lan—those which do not require a restriction-enzyme
`digestible primer—embodiments that, they argue, could
`be combined with Binladen. The Board declined to con-
`sider those embodiments because the cited “portions of
`Dhallan were not identified or discussed in the Petition or
`the accompanying Declarations.” Ariosa, at *10. In any
`event, the Board added, Ariosa’s explanation was lacking
`even as to those portions. Id.
`We see no error in the Board’s rejection of Ariosa’s re-
`liance, in its Reply submissions, on previously unidenti-
`fied portions of a prior-art reference to make a
`meaningfully distinct contention. Ariosa’s Petitions quote
`a portion of Dhallan that states: “Any method that pro-
`vides information on the sequence of a nucleic acid can be
`used . . . .” ’277 patent, col. 36, lines 6–19; see J.A. 189,
`215. The supporting declarations state that Dhallan
`teaches that the sequencing step can be performed using
`any method. J.A. 360–61 (quoting ’277 patent, col. 6, lines
`26–34); J.A. 919 (quoting ’277 patent, col. 36, lines 6–19).
`The Petitions and declarations, however, do no more than
`point to a generic statement in Dhallan that any sequenc-
`ing method can be used; they make no mention of how the
`choice of sequencing method influences the use of a re-
`striction-enzyme digestible primer, which occurs in the
`amplification step. ’277 patent, col. 36, lines 6–19. Not
`until Dr. Morton’s Reply declaration did Ariosa identify
`specific embodiments of Dhallan that do not use re-
`striction-enzyme digestible primers. J.A. 1479 (citing
`embodiments at ’277 patent, col. 11, line 61 through col.
`12, line 17; id., col. 12, lines 40–47; id., col. 13, line 66
`through col. 14, line 5; id., col. 13, lines 36–42; id., col. 14,
`lines 15–25).
`A governing regulation states that a Petition must
`identify “[t]he supporting evidence relied upon to support
`the challenge and the relevance of the evidence to the
`challenge raised, including identifying specific portions of
`
`IPR2013-00276
`Ariosa Exhibit 1050, pg. 16
`
`

`
`Case: 15-1215 Document: 54-2 Page: 17 Filed: 11/16/2015
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`the evidence that support the challenge.” 37 C.F.R.
`§ 42.104(b)(5). Further, “[t]he Board may exclude or give
`no weight to the evidence where a party has failed to state
`its relevance or to identify specific portions of the evidence
`that support the challenge” in the Petition. Id. That
`regulation reflects the combination of efficiency and
`fairness interests also embodied in the regulation limiting
`Reply submissions to matter responsive to the Patent
`Owner’s Response. Id. § 42.23(b). The Board must make
`judgments about whether a Petition identified the specific
`evidence relied on in a Reply and when a Reply contention
`crosses the line from the responsive to the new. The
`Board reasonably made those judgments here.
`C
`Ariosa challenges the adequacy of the Board’s consid-
`eration of Shoemaker—even though, as we have noted,
`the Board addressed Shoemaker throughout its analy