Court Opinion

ID: 3154931
Source: CourtListenerOpinion
Date Created: 2015-11-16 17:01:05.732667+00
Date Added: 2024-06-11T12:27:09.141269
License: Public Domain

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.
                ______________________
2              ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

    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
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.             3

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.”
4                ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

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
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.              5

       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
6               ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

        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
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.              7

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,
8              ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

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-
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.              9

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-
10                ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

     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).
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.              11

                         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
12              ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

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,
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.            13

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
14              ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

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
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.           15

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
16               ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.

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
ARIOSA DIAGNOSTICS   v. VERINATA HEALTH, INC.              17

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 analysis.
We need not decide, however, whether there are any
deficiencies in the Board’s consideration of arguments
about Shoemaker made and supported in a timely manner
by Ariosa. We are remanding the matter regardless. On
remand, the Board may decide whether its treatment of
Shoemaker should be left as is, supplemented, or revised.
                        CONCLUSION
    For the foregoing reasons, we vacate the Board’s find-
ing of nonobviousness and remand.
    No costs.
                VACATED AND REMANDED