Court Opinion

ID: 3173494
Source: CourtListenerOpinion
Date Created: 2016-01-29 17:01:03.272929+00
Date Added: 2024-06-11T12:17:29.107405
License: Public Domain

NOTE: This disposition is nonprecedential.

  United States Court of Appeals
      for the Federal Circuit
                 ______________________

     INDUSTRIAL TECHNOLOGY RESEARCH
                INSTITUTE,
                  Appellant

                            v.

  PACIFIC BIOSCIENCES OF CALIFORNIA, INC.,
                    Appellee
             ______________________

                       2015-1200
                 ______________________

    Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board, in Interference No.
105,970.
                  ______________________

               Decided: January 29, 2016
                ______________________

    ERIK R. PUKNYS, Finnegan, Henderson, Farabow,
Garrett & Dunner, LLP, Palo Alto, CA, argued for appel-
lant. Also represented by MICHAEL PAUL BARKER.

    EDWARD R. REINES, Weil, Gotshal & Manges LLP,
Redwood Shores, CA, argued for appellee. Also repre-
sented by MICHELE GAUGER, DEREK C. WALTER.
               ______________________
2       INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

    Before PROST, Chief Judge, LOURIE and WALLACH,
                    Circuit Judges.
LOURIE, Circuit Judge.
     Industrial Technology Research Institute and Ti-
Shiue Biotech, Inc. (collectively, “ITRI”) appeal from the
decision of the United States Patent and Trademark
Office Patent Trial and Appeal Board (“Board”) awarding
judgment to Pacific Biosciences of California, Inc. (“Pac-
Bio”) in Interference No. 105,970. Indus. Tech. Research
Inst. v. Pac. Biosciences of Cal., Inc., Interference No.
105,970, 2014 WL 4381078, at *1 (P.T.A.B. Sept. 3, 2014)
(“Board Decision”). The Board terminated the interfer-
ence after it determined that all of ITRI’s involved claims,
viz., claims 1–28 of U.S. Patent 8,486,630 (“the ’630
patent”), would have been obvious over the cited prior art,
and that PacBio, the senior party, was entitled to the
benefit of the filing date of its U.S. Provisional Applica-
tion 61/201,551 (“the ’551 application”) because that
application adequately described an embodiment of the
interference Count. Id. at *31. For the reasons that
follow, we affirm in part, vacate in part, and remand for
further proceedings consistent with this opinion.
                       BACKGROUND
                             I
    The technology at issue relates to methods of detect-
ing modified bases in nucleic acids. Deoxyribonucleic acid
(“DNA”) is a polymeric molecule having repeating units of
nucleotide bases—adenine (“A”), guanine (“G”), cytosine
(“C”), and thymine (“T”)—that are covalently linked
together via a sugar-phosphate backbone. DNA carries
genetic information in the sequence of those bases. DNA
also carries epigenetic information when one or more
bases are chemically modified. For example, C at a given
position in the DNA sequence may be naturally methylat-
ed and instead exist as 5-methylcytosine (“mC”). Such
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES        3

DNA methylation plays an important role in the regula-
tion of gene expression. ’630 patent col. 2 ll. 14–15.
Detecting modified bases in the DNA sequence would
facilitate the further study of their epigenetic effects.
    DNA usually exists in a double-stranded form, with
two strands coiled around each other in a double helix.
The two strands are often referred to as the “forward” and
“reverse” strands. In the double helix, each base on one
strand pairs with a base on the other strand according to
the Watson-Crick base pairing rules—A pairs with T, and
C with G. Thus, the forward and reverse strands typical-
ly have complementary sequences.
     A DNA sequence may be determined using sequenc-
ing-by-synthesis (“SBS”) methods. During DNA synthe-
sis, a parent strand is separated from its complement, and
an enzyme catalyzes the synthesis of a new complemen-
tary strand by adding nucleotides, one at a time, to that
new strand, using the parent strand as a template and
pairing bases according to the Watson-Crick rules. The
SBS technique monitors the order of nucleotide addition
to the growing new strand, and from that deduces the
sequence of the complementary template strand.
    Traditional SBS methods might not readily distin-
guish a base from its modified form. For example, C and
mC would both pair with G during SBS. Detecting the

addition of a G to the growing new strand only suggests
that either C or mC is at the corresponding position of the
template strand. According to ITRI, some prior-art meth-
ods relied on bisulfite conversion to distinguish C from
mC. Appellant’s Br. 2, 10–11. Thus, one first obtains a

reference sequence of the DNA being studied. A sample of
that DNA is then treated with bisulfite, which converts C
to uracil (“U”), but does not affect mC or other bases. The
bisulfite-treated DNA is then sequenced. Because U pairs
preferentially with A, not G, comparing the bisulfite-
treated DNA sequence with the untreated reference
4       INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

sequence would reveal the positions of the C-to-U conver-
sion, whereas the mC positions would show no change,
thus distinguishing C from mC in the DNA sequence.
                             II
    ITRI owns the ’630 patent, which claims a method of
determining the position of at least one modified base in a
double-stranded nucleic acid. Claim 24 is representative
and reads as follows: 1
    24. A method of determining a sequence of a dou-
        ble-stranded nucleic acid sample and a posi-
        tion of at least one modified base in the
        sequence, comprising:
        a. locking the forward and reverse strands of
           the nucleic acid sample together to form a
           circular pair-locked molecule;
        b. obtaining sequence data of the circular
           pair-locked molecule via single molecule
           sequencing, wherein sequence data com-
           prises sequences of the forward and re-
           verse strands of the circular pair-locked
           molecule; and
        c. determining the sequence of the double
           stranded nucleic acid sample and the posi-
           tion of the at least one modified base in the
           sequence of the double stranded nucleic ac-
           id sample by comparing the sequences of
           the forward and reverse strands of the cir-
           cular pair-locked molecule, wherein at
           least one modified base in the double-
           stranded nucleic sample is paired with a

    1    As indicated infra, the sole count of the interfer-
ence is identical to claim 24 of the ’630 patent.
6        INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

     The ’630 patent describes the bisulfite conversion of a
CPLM as one embodiment of the methods for detecting
modified bases, id. col. 23 ll. 44–65, col. 26, ll. 10–23, and
illustrates in Figure 5B, which is shown below, a bisulfite-
treated CPLM with matched mC-G and mismatched G-U
base pairs, id. col. 6 ll. 16–23.

Id. fig.5B.
     Additionally, claim 23 of the ’630 patent requires that
the forward and reverse strands of the double-stranded
nucleic acid be locked together by two nucleic acid inserts
of known sequences to form the CPLM. See id. fig.3A &
3B (depicting a CPLM made from the forward and reverse
strands 11 and 12 and two inserts 13 and 14). Because
sequencing data from a given experiment may not be
100% accurate, claim 23 provides that the CPLM is se-
quenced multiple times; that each set of the sequence
data of the inserts is scored by comparing the measured
sequence with the known sequence, id. col. 47 ll. 15–18;
and that a given set of the sequence data of the forward or
reverse strand is then accepted or rejected based on “the
scores of one or both of the sequences of the inserts imme-
diately upstream and downstream of the sample sequenc-
es,” id. col. 47 ll. 19–25.
    Claim 23 depends from claim 1; both claims are re-
produced below.
    1.   A method of determining a sequence of a dou-
         ble-stranded nucleic acid sample and a posi-
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES         7

        tion of at least one modified base in the se-
        quence, comprising:
        a. locking the forward and reverse strands
           together to form a circular pair-locked
           molecule;
        b. obtaining sequence data of the circular
           pair-locked molecule via single molecule
           sequencing, wherein the sequence data
           comprises sequences of the forward and
           reverse strands of the circular pair-locked
           molecule;
        c. determining the sequence of the double-
           stranded nucleic acid sample by comparing
           the sequences of the forward and reverse
           strands of the circular pair-locked mole-
           cule;
        d. altering the base-pairing specificity of ba-
           ses of a specific type in the circular pair-
           locked molecule to produce an altered cir-
           cular pair-locked molecule;
        e. obtaining the sequence data of the altered
           circular pair-locked molecule wherein the
           sequence data comprises sequences of the
           altered forward and reverse strands; and
        f. determining the positions of modified ba-
           ses in the sequence of the double-stranded
           nucleic acid sample by comparing the se-
           quences of the altered forward and reverse
           strands.
   23. The method of claim 1, wherein:
        the forward and reverse strands of the circu-
           lar pair-locked molecule are locked togeth-
           er by nucleic acid inserts;
8       INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

        the sequence data obtained in step (b) com-
           prise at least two copies of the sequence of
           the circular pair-locked molecule, each
           copy comprising sequences of first and sec-
           ond insert-sample units;
        the sequences of the first and second insert-
           sample units comprise insert sequences,
           which may be identical or non-identical,
           and oppositely oriented repeats of the se-
           quence of the nucleic acid sample; and
        the method further comprises:
        g. calculating scores of the sequences of at
           least four inserts contained in the se-
           quence data by comparing the sequences
           of the at least four inserts to the known
           sequences of the inserts;
        h. accepting or rejecting at least four of the
           repeats of the sequence of the nucleic acid
           sample contained in the sequence data ac-
           cording to the scores of one or both of the
           sequences of the inserts immediately up-
           stream and downstream of the sample se-
           quences, subject to the condition that at
           least one sample sequence in each orienta-
           tion is accepted;
        i. compiling an accepted sequence set com-
           prising the at least one sample sequence in
           each orientation accepted in step (g); and
        j. determining the sequence of the nucleic
           acid sample using the accepted sequence
           set.
Id. col. 45 ll. 24–47, col. 47 ll. 3–30 (emphasis added).
    Lastly, claims 27 and 28 of the ’630 patent require the
use of a “nucleotide analog that discriminates between a
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES         9

base and its modified form” in sequencing. Id. col. 48 ll.
28–33, 45–50. The ’630 patent describes such a compound
as a “discriminating analog” that “pairs preferentially
with one but not the other of the base and its modified
form.” Id. col. 24 ll. 15–19. The ’630 patent also provides
examples of “discriminating analogs” that were known in
the art. Id. col. 24 l. 42–col. 25 l. 24 (citing U.S. Patent
7,399,614). Those examples are base-linked analogs,
meaning that they have bulky groups chemically linked to
the base moiety, allowing them to pair preferentially with
a base or its modified form during sequencing. Claim 27
is representative of those two claims and reads as follows:
   27. A method of determining a sequence of a dou-
       ble-stranded nucleic acid sample and a posi-
       tion of at least one modified base in the
       sequence, comprising:
        a. locking the forward and reverse strands
           together to form a circular pair-locked
           molecule;
        b. obtaining sequence data of the circular
           pair-locked molecule via single molecule
           sequencing, wherein the sequence data
           comprises sequences of the forward and
           reverse strands of the circular pair-locked
           molecule;
        c. determining the sequence of the double-
           stranded nucleic acid sample by compar-
           ing the sequences of the forward and re-
           verse strands of the circular pair-locked
           molecule;
        d. obtaining sequencing data of the circular
           pair-locked molecule via single molecule
           sequencing, wherein at least one nucleotide
           analog that discriminates between a base
           and its modified form is used to obtain se-
10       INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

            quence data comprising at least one posi-
            tion wherein the at least one differentially
            labeled nucleotide analog was incorpo-
            rated; and
         e. determining the positions of modified ba-
            ses in the sequence of the double-stranded
            nucleic acid sample by comparing the se-
            quences of the forward and reverse
            strands.
Id. col. 48 ll. 15–37 (emphasis added).
                            III
    PacBio owns by assignment U.S. Patent Application
13/633,673 (“the ’673 application”) and U.S. Patent Appli-
cation 13/930,178 (“the ’178 application”). PacBio copied
the ’630 patent claims into its ’673 application to provoke
an interference with ITRI. 2 In October 2013, the Board
declared Interference No. 105,970 between PacBio’s ’673
application and ITRI’s ’630 patent. Three months later,
PacBio’s ’178 application was added to the interference.
    The interference involves a sole count corresponding
to all twenty-eight claims of ITRI’s ’630 patent and all
pending claims of PacBio’s ’673 and ’178 applications.
The Count is identical to claim 24 of the ’630 patent.
    When declaring the interference, the Board accorded
PacBio the benefit of the ’551 application, filed on Decem-
ber 11, 2008, and accorded ITRI the benefit of an applica-

     2  The parties do not dispute that ITRI’s ’630 patent
and PacBio’s ’673 and ’178 applications all have effective
filing dates before the enactment of the Leahy-Smith
America Invents Act (“AIA”), Pub. L. No. 112-29, 125 Stat.
284 (2011). The pre-AIA versions of 35 U.S.C. §§ 102,
103, and 112 therefore apply in this appeal. See Pub. L.
No. 112-29, § 3(n)(1), 125 Stat. at 293.
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES        11

tion filed on April 7, 2009. Based on those filing dates,
the Board designated PacBio as the senior party.
    The parties then filed preliminary motions, including
ITRI’s motion seeking to rescind the benefit of PacBio’s
’551 application (“rescind motion”) and PacBio’s motion
alleging that all claims of ITRI’s ’630 patent would have
been obvious in view of the prior art (“obviousness mo-
tion”). The prior art asserted by PacBio against ITRI’s
’630 patent included: (1) U.S. Patent 8,153,375 (“the ’375
patent”), assigned to PacBio; (2) PacBio’s Cold Spring
Harbor Personal Genomes Meeting Presentation, dated
October 12, 2008 (“the Personal Genomes presentation”);
(3) Laird et al., Hairpin-bisulfite PCR: Assessing epigenet-
ic methylation patterns on complementary strands of
individual DNA molecules, 101 Proc. Nat’l Acad. Sci. 204
(2004) (“Laird”); (4) Matsumura et al., Photochemical
transition of 5-methylcytosine to thymine by DNA photo-
ligation, 51 Nucleic Acids Symp. Series 233 (2007)
(“Matsumura”); and (5) U.S. Patent 7,399,614 (“the ’614
patent”).
    In a written decision on September 3, 2014, the Board
granted PacBio’s obviousness motion and denied ITRI’s
rescind motion. In granting PacBio’s obviousness motion,
the Board concluded that all claims of ITRI’s ’630 patent
would have been obvious in view of the ’375 patent, Laird,
and Matsumura. Board Decision, 2014 WL 4381078, at
*20. Although the Board cited Matsumura, its obvious-
ness analysis did not rely on any specific teachings of
Matsumura. The Board also did not rely on the ’614
patent cited by PacBio. Moreover, the Board did not
consider the Personal Genomes presentation, after finding
that it was not prior art under 35 U.S.C. § 102(b). Id. at
*13 n.27. Thus, the Board relied only on the ’375 patent
and Laird as prior art in its obviousness analysis.
    First, as to claim 24, which the parties regarded as
representative of most of the claims of the ’630 patent, the
12      INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

Board noted that ITRI did not dispute that the ’375
patent taught steps (a) and (b) of claim 24. The Board
then found that Laird taught step (c), and thus concluded
that claim 24 would have been obvious in view of the ’375
patent and Laird. Id. at *20–21. Second, the Board
rejected ITRI’s argument that the prior art did not teach
step (h) of claim 23; instead, the Board found that the ’375
patent and Laird taught that limitation. Id. at *22. Last,
as to claims 27 and 28, which require a nucleotide analog
that discriminates between a base and its modified form,
the Board concluded that those claims would have been
obvious because “Laird teaches such a method [of] dis-
criminating between methylated and non-methylated
cytosines.” Id. at *22–23.
    The Board accordingly found all claims of the ’630 pa-
tent to be unpatentable as obvious because “[t]he com-
bined cited prior art references teach or suggest all of the
limitations of the claims of the ’630 patent” and “a person
of ordinary skill in the art would be motivated to combine
the references to increase the accuracy of the invention,
particularly with respect to discriminating between
methylated and demethylated cytosine bases.” Id. at *23.
The Board did not opine on whether the references cited
by PacBio would be prior art to PacBio’s own claims, thus
rendering them similarly unpatentable as obvious, even
though the parties disputed that issue. J.A. 269–70, 346,
421, 750–52.
    In denying ITRI’s rescind motion, the Board found
that PacBio was entitled to the benefit of the filing date of
the ’551 application because that application provided an
adequate written description of an embodiment of the
Count. Board Decision, 2014 WL 4381078, at *28–31. In
particular, the Board found that the ’551 application
teaches step (c) of the Count, in part, because the applica-
tion explicitly states that “‘sequence reads from the sense
or ‘forward’ strand can be compared to sequence reads
from the antisense or ‘reverse’ strand for the same nucleic
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES       13

acid template to further validate the existence of one or
more modified bases in the template nucleic acid.’” Id. at
*28–29 (quoting ’551 application ¶ 17).
    The Board entered judgment against ITRI. Id. at *1.
ITRI then appealed to this court. We have jurisdiction
under 28 U.S.C. § 1295(a)(4)(A). See Leahy-Smith Ameri-
ca Invents Act Technical Corrections, Pub. L. No. 112-274,
§ 1(k)(3), 126 Stat. 2456, 2458 (2013).
                       DISCUSSION
        I. OBVIOUSNESS OF ITRI’S PATENT CLAIMS
    We review the Board’s legal determinations de novo,
In re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), and the
Board’s factual findings underlying those determinations
for substantial evidence, In re Gartside, 203 F.3d 1305,
1316 (Fed. Cir. 2000). A finding is supported by substan-
tial evidence if a reasonable mind might accept the evi-
dence to support the finding. Consol. Edison Co. v.
NLRB, 305 U.S. 197, 229 (1938).
    Obviousness is a question of law based on underlying
factual findings, In re Baxter, 678 F.3d 1357, 1361 (Fed.
Cir. 2012), including what a reference teaches, In re
Beattie, 974 F.2d 1309, 1311 (Fed. Cir. 1992), the exist-
ence of a reason to combine references, In re Hyon, 679
F.3d 1363, 1365–66 (Fed. Cir. 2012), and whether the
prior art teaches away from the claimed invention, In re
Mouttet, 686 F.3d 1322, 1330 (Fed. Cir. 2012).
                A. Claims 1–22 and 24–26
    ITRI argues that the Board erred in finding that
Laird teaches determining the position of a modified base
by comparing the sequences of the forward and reverse
14       INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

strands as required by step (c) of claim 24. 3 According to
ITRI, researchers in Laird used conventional methods to
determine the positions of modified bases, by comparing
the sequences of bisulfite-treated and untreated versions
of the same strand, not the forward and reverse strands of
the same molecule as claimed by ITRI. ITRI asserts that
the Board improperly engaged in hindsight analysis by
speculating that a skilled artisan would have understood
that mismatches in the sequences of the forward and
reverse strands would indicate modified base positions.
According to ITRI, only the ’630 patent, not Laird or any
other prior art, teaches using mismatches to detect modi-
fied bases.
    PacBio responds that the claims do not require using
mismatches to detect modified bases because a preferred
embodiment of the ’630 patent, involving bisulfite conver-
sion of C (but not mC) to U, uses matches of mC to G to
detect the mC positions. Appellee’s Br. 29–33 (citing ’630
patent col. 26 ll. 10–22). PacBio alternatively argues that,
even if the use of mismatches were required, the claims
would still have been obvious because substantial evi-
dence supports the Board’s finding that Laird teaches
that limitation. PacBio additionally argues that a person
of skill in the art would have been motivated to combine
the prior art to practice the claimed method and achieve a
predictable result, that one would have had a reasonable
expectation of success in doing so, and that there is no
evidence of objective indicia of nonobviousness.
    We agree with PacBio that the Board did not err in its
obviousness determination as to claims 1–22 and 24–26

     3  ITRI relies only on limitations in claim 24 to chal-
lenge the obviousness determination as to claims 1–22
and 24–26. See Appellant’s Br. 29. Those claims there-
fore stand or fall together with claim 24. In re Kaslow,
707 F.2d 1366, 1376 (Fed. Cir. 1983).
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES        15

because Laird suggests using mismatches in the sequenc-
es of the forward and reverse strands to determine modi-
fied base positions. ITRI does not dispute that the ’375
patent discloses steps (a) and (b) of claim 24. Nor does
ITRI challenge the Board’s finding of a motivation to
combine the ’375 patent and Laird. The only question is
then whether substantial evidence supports the Board’s
finding that Laird teaches step (c) of claim 24, and we
conclude that it does.
    As an initial matter, the record shows that the Board
did not formally construe the claims. In the background
section of the Board’s written decision, it informally
interpreted step (c) of claim 24, or the Count, as requiring
the use of mismatches in determining modified base
positions, which is what ITRI proposed. Board Decision,
2014 WL 4381078, at *3. Applying that claim interpreta-
tion, the Board decided the obviousness motion and the
rescind motion against ITRI. Id. at *21, *30.
    The Board’s claim interpretation is consistent with
the claim language and specification of the ’630 patent.
Contrary to PacBio’s arguments, that interpretation does
not exclude the bisulfite method disclosed in the ’630
patent, in which bisulfite converts C, but not mC, to U in a
CPLM. When comparing the sequences of the forward
and reverse strands of such a bisulfite-treated CPLM, one
would find both matched mC-G pairs and mismatched U-G
pairs. The bisulfite method does use mismatched U-G
pairs in distinguishing C from mC and in determining the
positions of modified bases, which may be either U or mC.
The parties do not otherwise allege error in the Board’s
claim interpretation. Accordingly, on this record, we
conclude that the Board did not err in interpreting step (c)
16       INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

of claim 24, or the Count, as requiring the use of mis-
matches in determining modified base positions. 4
    Although we agree with ITRI on the proper interpre-
tation of step (c) of claim 24, we nevertheless conclude
that substantial evidence supports the Board’s finding
that the disclosure of Laird would have suggested that
claim limitation to a person of ordinary skill in the art.
Laird teaches “hairpin-bisulfite PCR.” J.A. 722. It ex-
plains that “[b]isulfite conversion . . . provides information
on the methylation state of individual cytosines by con-
verting cytosine (but not 5-methylcytosine) to uracil . . . .”
J.A. 723. Thus, Laird teaches that modified bases can be
detected through the use of bisulfite treatment.
     As disclosed in Laird, a double-stranded DNA was li-
gated on one end with a hairpin linker, and the covalently
linked forward and reverse strands were treated with
bisulfite and then sequenced. Id. According to Laird,
“[f]or purposes of analysis and presentation, the output
sequence was folded, using word-processing software, into
a hairpin conformation so that both strands align.” Id.
(emphases added). Laird depicts in Figure 2 several pairs
of forward and reverse strands side-by-side that have
mismatches in the sequences of the forward and reverse
strands as a result of the bisulfite treatment. J.A. 725.
Laird explains that “[w]ith hairpin-bisulfite PCR, we can
assess the methylation status on the bottom strand of
each hypermethylated allele for which we have top-strand
data,” and that “we can distinguish between symmetrical
and asymmetrical patterns of methylation for each of the

     4  PacBio filed a motion in this court to strike cer-
tain arguments made in ITRI’s reply brief, relating to the
prosecution history of the ’630 patent, as improperly
raised for the first time on appeal. Because our decision
does not turn on those arguments, we dismiss PacBio’s
motion as moot.
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES         17

CpG/CpG dyads.” J.A. 724 (emphases added). Moreover,
Figure 2D shows several asymmetrical hemimethylated
CpG/CpG dyads, in which one strand of the DNA has a mC
and the other has a C. J.A. 725.
    Substantial evidence therefore supports the Board’s
finding that “Laird teaches that methylated and un-
methylated [CpG] dyads in a bisulfite-treated DNA se-
quence can be identified by the matching or mismatching
of cytosines in the forward and reverse strand sequence
data,” Board Decision, 2014 WL 4381078, at *20, and that
“Laird explicitly teaches looking for guanine-thymine
mismatches as evidence of non-methylated cytosine in a
forward or reverse strand locus,” id. at *21. We therefore
conclude that the Board did not err in finding that Laird
would have suggested to a person of ordinary skill in the
art that mismatched base pairs in the sequences of the
forward and reverse strands may be used to determine
the positions of modified bases in double-stranded DNA.
    Accordingly, we affirm the Board’s determination that
claims 1–22 and 24–26 would have been obvious over the
’375 patent and Laird.
                        B. Claim 23
    ITRI argues that the Board additionally erred in find-
ing claim 23 obvious because the Board failed to find that
the prior art taught step (h) of claim 23, which requires
accepting or rejecting a given data set of a DNA sample
sequence based on the score calculated for an insert se-
quence immediately upstream or downstream from the
sample sequence. ITRI contends that the Board failed to
otherwise point to any record evidence to support its
finding that the prior art taught step (h).
    PacBio responds that step (h) of claim 23 would have
been obvious in view of the ’375 patent. PacBio argues
that the level of skill in the art was high and that, even if
the ’375 patent does not precisely teach step (h), a skilled
18      INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

artisan would have nonetheless found the differences
between the claimed invention and the ’375 patent to be
insubstantial and therefore obvious.
     We agree with ITRI that the Board did not sufficiently
address whether the prior art teaches step (h) of claim 23
or otherwise would have rendered that limitation obvious.
It is undisputed that claim 23 requires that, when analyz-
ing multiple reads of the CPLM sequence, one accepts or
rejects a given data set of the forward or reverse strand
sequence based on the score of a different sequence—the
insert sequence upstream or downstream from the for-
ward or reverse strand sequence. But the Board’s cursory
obviousness analysis with respect to claim 23 lacks any
indication that the Board considered that claim limitation
in view of the prior art. The Board’s analysis seems to
mainly focus on using multiple reads of one position in the
sequence to determine the consensus sequence of that
same position. Board Decision, 2014 WL 4381078, at *22.
     It may be true that, in view of the cited prior art and
the level of ordinary skill in the relevant art, the differ-
ences between step (h) of claim 23 and the prior art would
have been insubstantial. But the scope and content of the
prior art and the differences between the prior art and the
claimed invention are issues of fact to be decided by the
Board, not this court. Cooper v. Ford Motor Co., 748 F.2d
677, 679 (Fed. Cir. 1984). The Board did not make suffi-
cient factual findings in its written decision or otherwise
point to evidence that a skilled artisan would have ac-
cepted or rejected a sample sequence based on the score of
a different insert sequence that is upstream or down-
stream from the sample sequence. We therefore vacate
the obviousness determination as to claim 23 and remand
for further proceedings at the Board.
                   C. Claims 27 and 28
   ITRI argues that the Board erred in finding claims 27
and 28 obvious because neither the ’375 patent nor Laird,
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES        19

which the Board relied on, discloses the use of a discrimi-
nating nucleotide analog as required by the claims. ITRI
also contends that the Board provided no explanation for
why the missing claim limitation would nonetheless have
been obvious. ITRI also argues that the Board improperly
disregarded evidence that the Personal Genomes presen-
tation taught away from using base-linked analogs, which
include discriminating nucleotide analogs, and thus would
have discouraged a skilled artisan from combining the
’375 patent with a discriminating nucleotide analog.
    PacBio responds that its obviousness arguments be-
fore the Board were based on the combination of the ’375
patent with the ’614 patent, not Laird, and that ITRI does
not dispute that the ’614 patent teaches discriminating
nucleotide analogs. PacBio thus argues that, to the
extent the Board erred in finding that Laird teaches a
discriminating nucleotide analog, that error is harmless
because claims 27 and 28 would have been obvious in
view of the ’375 and ’614 patents. PacBio also argues that
the Personal Genomes presentation does not teach away
from the use of a discriminating nucleotide analog or the
use of a base-linked nucleotide analog in general.
     We agree with ITRI that the Board erred in conclud-
ing that claims 27 and 28 would have been obvious over
the combination of the ’375 patent and Laird. The claims
require the use of a “nucleotide analog that discriminates
between a base and its modified form.” The ’630 patent
explains that a “discriminating analog . . . pairs preferen-
tially with one but not the other of the base and its modi-
fied form.” ’630 patent col. 24 ll. 15–19. The Board did
not find, and PacBio does not contend, that either the ’375
patent or Laird teaches such a discriminating nucleotide
analog. The Board only found that Laird taught “discrim-
inating between methylated and non-methylated cyto-
sines.” Board Decision, 2014 WL 4381078, at *23. But
Laird’s method uses bisulfite to convert C to U and then
distinguishes C from mC for the fact that U pairs with A
20       INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

and mC pairs with G. The Board did not otherwise indi-
cate why the “discriminating nucleotide analog” limitation
would have been obvious in view of the record evidence.
    Although the ’614 patent, cited by PacBio, does dis-
close discriminating nucleotide analogs, the parties dis-
pute whether the Personal Genomes presentation teaches
away from combining the ’375 and ’614 patents. ITRI
argued to the Board that the Personal Genomes presenta-
tion taught away from using base-linked analogs in the
sequencing methods described in the ’375 patent. J.A.
344. But the Board did not consider the disclosure of the
Personal Genomes presentation, after finding that it was
not prior art under 35 U.S.C. § 102(b). Board Decision,
2014 WL 4381078, at *13 n.27. The Board did not consid-
er whether the Personal Genomes presentation would
qualify as prior art under other subsections of § 102, such
as § 102(a).
    Whether the prior art teaches away from the claimed
invention is a question of fact. Mouttet, 686 F.3d at 1330.
The Board did not consider some of the cited prior art,
including the Personal Genomes presentation, and it did
not properly determine whether a skilled artisan would
have pursued the method of claims 27 and 28, which uses
a discriminating nucleotide analog. We therefore vacate
the obviousness determination as to claims 27 and 28 and
remand for further proceedings at the Board.
        II.   CROSS-APPLICABILITY OF THE PRIOR ART
   Section 41.207(c) of Title 37 of the Code of Federal
Regulations provides:
     When a motion for judgment of unpatentability
     against an opponent’s claim on the basis of prior
     art is granted, each of the movant’s claims corre-
     sponding to the same count as the opponent’s
     claim will be presumed to be unpatentable in view
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES           21

    of the same prior art unless the movant in its mo-
    tion rebuts this presumption.
37 C.F.R. § 41.207(c) (cross-applicability of prior art).
    Before the Board, PacBio asserted the ’375 patent,
which it owns, as prior art under 35 U.S.C. § 102(e), and
it sought to establish common ownership of the ’375
patent and its ’673 and ’178 applications under § 103(c),
in order to disqualify the ’375 patent as prior art against
itself. When the Board granted PacBio’s obviousness
motion, invalidating all of ITRI’s claims, it did not opine
on the patentability of PacBio’s claims or otherwise indi-
cate whether PacBio has overcome the presumption of
cross-applicability of the cited prior art.
    ITRI argues that the Board erred by failing to hold
PacBio’s claims unpatentable pursuant to 37 C.F.R.
§ 41.207(c). ITRI also argues that PacBio failed to rebut
the presumption of cross-applicability, and that the Board
incorrectly analyzed common ownership under 35 U.S.C.
§ 103(c). PacBio responds that it has rebutted any pre-
sumption of cross-applicability by explaining to the Board
that the ’375 patent does not preclude patentability of its
claims under § 103(c) and by submitting a declaration
with its reply. PacBio also argues that the Board properly
exercised its discretion not to apply the presumption.
     On this record, it is unclear whether the Board implic-
itly determined that PacBio has overcome the presump-
tion of cross-applicability or whether the Board decided
not to apply the prior art to PacBio’s claims for some other
reason. Because we affirm the obviousness determination
as to claims 1–22 and 24–26 of ITRI’s ’630 patent and
remand the case for further determinations as to claims
23, 27, and 28 of that patent, the Board will have another
opportunity to address the cross-applicability issue.
   The record does show, however, that the Board might
have misunderstood what was required to disqualify prior
22       INDUSTRIAL TECH. RESEARCH INST.    v. PAC. BIOSCIENCES

art under 35 U.S.C. § 103(c). In an August 2014 decision
denying ITRI’s motion to strike PacBio’s reply brief and
accompanying declaration, the Board reasoned:
     It is therefore evident that, regardless of who the
     inventors of the ’375 patent and ’673 and ’178 ap-
     plications were, the Moore Declaration provides
     evidence in support of PacBio’s contention that
     the patent and applications had been assigned to,
     and were owned by, PacBio. That PacBio is the
     assignee of the ’375 patent and ’673 and ’178 ap-
     plications, no matter who the inventors were, is not
     disputed by the parties. To that extent, viz., the
     issue of common ownership, the Board will con-
     sider the evidentiary weight of the Moore Declara-
     tion in support of PacBio’s arguments. With
     respect to inventorship, the Board will defer that
     issue to the priority phase of the interference . . . .
Indus. Tech. Research Inst. v. Pac. Biosciences of Cal.,
Inc., Interference No. 105,970, Paper 166, at *9 (P.T.A.B.
Aug. 11, 2014) (first emphasis in original) (second and
third emphases added) (J.A. 480).
    It appears that the Board might have misapplied
§ 103(c) by reasoning that the assessment of common
ownership may be based on evidence of common owner-
ship by assignment, even if the assignment occurred after
the application filing date. 35 U.S.C. § 103(c) provides
that § 102(e) prior art does not preclude patentability if
“the subject matter [of the prior art] and the claimed
invention were, at the time the claimed invention was
made, owned by the same person or subject to an obliga-
tion of assignment to the same person” (emphasis added).
Accordingly, evidence of common ownership by assign-
ment after the application filing date does not establish
common ownership or an obligation to assign ownership
at the time of the invention.
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES         23

    We therefore remand for a determination of the cross-
applicability of the cited prior art to PacBio’s claims and,
if necessary, a proper analysis of common ownership of
the ’375 patent and the ’673 and ’178 applications.
   III. WRITTEN DESCRIPTION IN THE ’551 APPLICATION
    Sufficiency of written description is a question of fact,
which we review for substantial evidence. Ariad Pharm.,
Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir.
2010) (en banc). Claims must be sufficiently supported by
the written description of a patent, such that the disclo-
sure “reasonably conveys to those skilled in the art that
the inventor had possession of the claimed subject matter
as of the filing date.” Id. To receive the benefit of an
earlier application in an interference, the application
must contain an adequate written description of at least
one embodiment of the count. Tobinick v. Olmarker, 753
F.3d 1220, 1227 (Fed. Cir. 2014).
     ITRI argues that the Board erred in designating Pac-
Bio the senior party because the ’551 application lacks a
written description of the Count, in particular, any ex-
press or inherent disclosure of using mismatched base
pairs to determine modified base positions. According to
ITRI, paragraph 17 of the ’551 application, including its
reference to comparing the forward and reverse strands,
merely describes using base-pair matches, not mismatch-
es, to confirm the reliability of sequencing data. ITRI also
asserts that the ’551 application disclaims the bisulfite
embodiment of the Count because the ’551 application
states that its methods do not “rel[y] on the similarity of
uracil to thymine.” Appellant’s Br. 41 (quoting ’551
application ¶ 23). ITRI explains that the Count relies on
the similarity of U and T, because, when U is the modified
base after bisulfite treatment, the claimed method relies
on the fact that both U and T pair with A in sequencing.
    PacBio responds that the Board correctly found that
the ’551 application discloses an embodiment of the Count
24      INDUSTRIAL TECH. RESEARCH INST.   v. PAC. BIOSCIENCES

because it expressly discloses (1) a CPLM DNA sequenc-
ing template, (2) the use of bisulfite treatment, and (3) the
comparison of forward and reverse strands of the CPLM
to identify modified bases. PacBio argues that the Count
does not require using mismatches to determine the
positions of modified bases. PacBio also argues in the
alternative that, even if the Count did require the use of
mismatches, the Board’s factual finding of adequate
written description is supported by substantial evidence,
which includes the ’551 application’s express disclosures
and the detailed testimony of PacBio’s expert witness
explaining the disclosures of the ’551 application.
    As indicated supra, we conclude that the Board
properly interpreted the Count as requiring the use of
mismatched base pairs in detecting modified base posi-
tions. Under that construction, we conclude that substan-
tial evidence supports the Board’s finding that the ’551
application adequately describes an embodiment of the
Count. The ’551 application describes methods of detect-
ing modified bases. The application discloses a CPLM
template, as well as the use of bisulfite to convert C, but
not mC, to U. J.A. 918–20. The application defines “modi-
fied bases” as including “methylated bases” and “bisulfite-
converted bases.” J.A. 919.
    Importantly, the application states in paragraph 17
that “sequence reads from the sense or ‘forward’ strand
can be compared to sequence reads from the antisense or
‘reverse’ strand for the same nucleic acid template to
further validate the existence of one or more modified
bases in the template nucleic acid.” J.A. 918 (emphases
added). That is an explicit reference to comparing the
forward and reverse strands and using base-pair matches
and mismatches to detect modified bases. Although other
portions of the ’551 application describe prior-art consen-
sus sequencing technique, those disclosures do not alter
the explicit reference to “compar[ing]” the forward and
reverse strand sequences to determine “the existence of
INDUS. TECH. RESEARCH INST.   v. PAC. BIOSCIENCES      25

one or more modified bases.” Likewise, we find ITRI’s
argument that paragraph 23 of the application disclaims
the bisulfite embodiment of the Count to be unpersuasive.
    We therefore affirm the Board’s finding that the ’551
application provides an adequate written description of at
least one embodiment of the Count.
                       CONCLUSION
    We have considered the parties’ remaining argu-
ments, but find them unpersuasive. For the foregoing
reasons, we affirm the Board’s decision that claims 1–22
and 24–26 of ITRI’s ’630 patent would have been obvious
over the cited references and that PacBio’s ’551 applica-
tion contains an adequate written description of an em-
bodiment of the Count. Additionally, we vacate the
Board’s obviousness judgment as to claims 23, 27, and 28
of the ’630 patent and remand for a further determination
of the patentability of those claims and for the Board to
address the cross-applicability of the cited prior art to
PacBio’s involved claims.
  AFFIRMED IN PART, VACATED IN PART, AND
                REMANDED
                          COSTS
   No costs.