Opinion ID: 3173494
Heading Depth: 2
Heading Rank: 1

Heading: obviousness of itri’s patent claims

Text: 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).
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 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). INDUS. TECH. RESEARCH INST. v. PAC. BIOSCIENCES 15 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 . Applying that claim interpretation, the Board decided the obviousness motion and the rescind motion against ITRI. Id. at , . 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 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 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 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 , 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 . 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.
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 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 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 . 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.
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 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 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 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 . 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 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  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.