Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-15-01200/USCOURTS-ca13-15-01200-0/pdf.json

Parties Involved:
Industrial Technology Research Institute
Appellant
Pacific Biosciences of California, Inc.
Appellee

Document Text:

NOTE: This disposition is nonprecedential.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 appellant. Also represented by MICHAEL PAUL BARKER. 

EDWARD R. REINES, Weil, Gotshal & Manges LLP, 

Redwood Shores, CA, argued for appellee. Also represented by MICHELE GAUGER, DEREK C. WALTER. 

______________________ 

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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 TiShiue 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. (“PacBio”) 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 interference 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 Application 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 detecting 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 methylated and instead exist as 5-methylcytosine (“mC”). Such 

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DNA methylation plays an important role in the regulation 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 typically have complementary sequences.

A DNA sequence may be determined using sequencing-by-synthesis (“SBS”) methods. During DNA synthesis, a parent strand is separated from its complement, and 

an enzyme catalyzes the synthesis of a new complementary 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 distinguish 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 methods 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 bisulfitetreated DNA sequence with the untreated reference 

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4 INDUSTRIAL TECH. RESEARCH INST. v. PAC. BIOSCIENCES

sequence would reveal the positions of the C-to-U conversion, 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 double-stranded nucleic acid sample and a position 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 comprises sequences of the forward and reverse strands of the circular pair-locked 

molecule; and 

c. determining the sequence of the double 

stranded nucleic acid sample and the position of the at least one modified base in the 

sequence of the double stranded nucleic acid sample by comparing the sequences of 

the forward and reverse strands of the circular pair-locked molecule, wherein at 

least one modified base in the doublestranded nucleic sample is paired with a 

1 As indicated infra, the sole count of the interference is identical to claim 24 of the ’630 patent.

 

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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 bisulfitetreated 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 sequenced 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 immediately upstream and downstream of the sample sequences,” id. col. 47 ll. 19–25. 

Claim 23 depends from claim 1; both claims are reproduced below. 

1. A method of determining a sequence of a double-stranded nucleic acid sample and a posiCase: 15-1200 Document: 61-2 Page: 6 Filed: 01/29/2016
INDUS. TECH. RESEARCH INST. v. PAC. BIOSCIENCES 7

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 doublestranded nucleic acid sample by comparing 

the sequences of the forward and reverse 

strands of the circular pair-locked molecule; 

d. altering the base-pairing specificity of bases of a specific type in the circular pairlocked molecule to produce an altered circular 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 bases in the sequence of the double-stranded 

nucleic acid sample by comparing the sequences of the altered forward and reverse 

strands. 

23. The method of claim 1, wherein: 

the forward and reverse strands of the circular pair-locked molecule are locked together by nucleic acid inserts; 

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the sequence data obtained in step (b) comprise at least two copies of the sequence of 

the circular pair-locked molecule, each 

copy comprising sequences of first and second insert-sample units; 

the sequences of the first and second insertsample units comprise insert sequences, 

which may be identical or non-identical, 

and oppositely oriented repeats of the sequence of the nucleic acid sample; and 

the method further comprises: 

g. calculating scores of the sequences of at 

least four inserts contained in the sequence 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 according to the scores of one or both of the 

sequences of the inserts immediately upstream and downstream of the sample sequences, subject to the condition that at 

least one sample sequence in each orientation is accepted; 

i. compiling an accepted sequence set comprising 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 

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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 double-stranded nucleic acid sample and a position 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 doublestranded nucleic acid sample by comparing the sequences of the forward and reverse 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 seCase: 15-1200 Document: 61-2 Page: 9 Filed: 01/29/2016
10 INDUSTRIAL TECH. RESEARCH INST. v. PAC. BIOSCIENCES

quence data comprising at least one position wherein the at least one differentially 

labeled nucleotide analog was incorporated; and 

e. determining the positions of modified bases in the sequence of the double-stranded 

nucleic acid sample by comparing the sequences 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 Application 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 December 11, 2008, and accorded ITRI the benefit of an applica2 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.

 

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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 motion”). 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 epigenetic 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 photoligation, 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 obviousness 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 

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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] discriminating between methylated and non-methylated 

cytosines.” Id. at *22–23. 

The Board accordingly found all claims of the ’630 patent to be unpatentable as obvious because “[t]he combined 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 application 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 

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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 America 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 substantial evidence if a reasonable mind might accept the evidence 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 existence 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 

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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 modified 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 conversion 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 evidence 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 challenge the obviousness determination as to claims 1–22 

and 24–26. See Appellant’s Br. 29. Those claims therefore stand or fall together with claim 24. In re Kaslow, 

707 F.2d 1366, 1376 (Fed. Cir. 1983).

 

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because Laird suggests using mismatches in the sequences of the forward and reverse strands to determine modified 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 interpretation, 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) 

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of claim 24, or the Count, as requiring the use of mismatches in determining modified base positions.4

Although we agree with ITRI on the proper interpretation 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 explains that “[b]isulfite conversion . . . provides information 

on the methylation state of individual cytosines by converting 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 ligated 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 certain 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.

 

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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 unmethylated [CpG] dyads in a bisulfite-treated DNA sequence 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 finding 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 sequence 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 

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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 analyzing 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 forward 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 differences 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 sufficient factual findings in its written decision or otherwise 

point to evidence that a skilled artisan would have accepted or rejected a sample sequence based on the score of 

a different insert sequence that is upstream or downstream 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, 

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which the Board relied on, discloses the use of a discriminating 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 presentation 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 before 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 concluding 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 preferentially with one but not the other of the base and its modified 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 “discriminating between methylated and non-methylated cytosines.” 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 

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20 INDUSTRIAL TECH. RESEARCH INST. v. PAC. BIOSCIENCES

and mC pairs with G. The Board did not otherwise indicate why the “discriminating nucleotide analog” limitation 

would have been obvious in view of the record evidence.

Although the ’614 patent, cited by PacBio, does disclose discriminating nucleotide analogs, the parties dispute whether the Personal Genomes presentation teaches 

away from combining the ’375 and ’614 patents. ITRI 

argued to the Board that the Personal Genomes presentation 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 consider 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 corresponding to the same count as the opponent’s 

claim will be presumed to be unpatentable in view 

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INDUS. TECH. RESEARCH INST. v. PAC. BIOSCIENCES 21

of the same prior art unless the movant in its motion 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 indicate 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 presumption 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 implicitly determined that PacBio has overcome the presumption 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 

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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 applications 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 applications, no matter who the inventors were, is not 

disputed by the parties. To that extent, viz., the 

issue of common ownership, the Board will consider the evidentiary weight of the Moore Declaration 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 ownership 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 obligation of assignment to the same person” (emphasis added). 

Accordingly, evidence of common ownership by assignment after the application filing date does not establish 

common ownership or an obligation to assign ownership 

at the time of the invention. 

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INDUS. TECH. RESEARCH INST. v. PAC. BIOSCIENCES 23

We therefore remand for a determination of the crossapplicability 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 disclosure “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 PacBio the senior party because the ’551 application lacks a 

written description of the Count, in particular, any express 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 mismatches, 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 

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24 INDUSTRIAL TECH. RESEARCH INST. v. PAC. BIOSCIENCES

because it expressly discloses (1) a CPLM DNA sequencing 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 positions. Under that construction, we conclude that substantial evidence supports the Board’s finding that the ’551 

application adequately describes an embodiment of the 

Count. The ’551 application describes methods of detecting 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 “modified bases” as including “methylated bases” and “bisulfiteconverted 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 consensus sequencing technique, those disclosures do not alter 

the explicit reference to “compar[ing]” the forward and 

reverse strand sequences to determine “the existence of 

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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 arguments, 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 application contains an adequate written description of an embodiment 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.

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