United States Court of Appeals
`for the Federal Circuit
`______________________
`
`AJINOMOTO CO., INC., AJINOMOTO HEARTLAND
`INC.,
`Appellants
`
`v.
`
`INTERNATIONAL TRADE COMMISSION,
`Appellee
`
`CJ CHEILJEDANG CORP., CJ AMERICA, INC., PT
`CHEILJEDANG INDONESIA,
`Intervenors
`
`- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
`
`CJ CHEILJEDANG CORP., CJ AMERICA, INC., PT
`CHEILJEDANG INDONESIA,
`Appellants
`
`v.
`
`INTERNATIONAL TRADE COMMISSION,
`Appellee
`
`AJINOMOTO CO., INC., AJINOMOTO HEARTLAND
`INC.,
`Intervenors
`______________________
`
`2018-1590, 2018-1629
`______________________
`
`
`

`

`2
`
`AJINOMOTO CO., INC. v. ITC
`
`Appeals from the United States International Trade
`Commission in Investigation No. 337-TA-1005.
`______________________
`
`Decided: August 6, 2019
`______________________
`
`JOHN D. LIVINGSTONE, Finnegan, Henderson, Farabow,
`Garrett & Dunner, LLP, Atlanta, GA, argued for Ajinomoto
`Co., Inc., Ajinomoto Heartland Inc. Also represented by
`MARTIN DAVID WEINGARTEN; CHARLES E. LIPSEY, Reston,
`VA; MAREESA ARNITA FREDERICK, CORA RENAE HOLT,
`BARBARA RUDOLPH, Washington, DC.
`
` HOUDA MORAD, Office of General Counsel, United
`States International Trade Commission, Washington, DC,
`argued for appellee. Also represented by SIDNEY A.
`ROSENZWEIG, DOMINIC L. BIANCHI, WAYNE W. HERRINGTON.
`
` JAMES F. HALEY, JR., Haley Guiliano LLP, New York,
`NY, argued for CJ CheilJedang Corp., CJ America, Inc., PT
`CheiJedang Indonesia. Also represented by STEVEN PEPE,
`Ropes & Gray LLP, New York, NY; MATTHEW RIZZOLO,
`Washington, DC.
` ______________________
`
`Before DYK, MOORE, and TARANTO, Circuit Judges.
`Opinion for the court filed by Circuit Judge TARANTO.
`Opinion concurring in part and dissenting in part filed by
`Circuit Judge DYK.
`TARANTO, Circuit Judge.
`Ajinomoto Co., Inc. and Ajinomoto Heartland Inc. (col-
`lectively, Ajinomoto)
`filed a complaint against CJ
`CheilJedang Corp., CJ America, Inc., and PT CheilJedang
`Indonesia (collectively, CJ) with the International Trade
`Commission, alleging that CJ was importing certain
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`3
`
`products that infringed Ajinomoto’s U.S. Patent No.
`7,666,655. CJ used several strains of Escherichia coli bac-
`teria to produce L-tryptophan products, which it then im-
`ported
`into the United States.
` The Commission
`determined that CJ’s earlier strains did not infringe but
`that CJ’s two later strains did. The Commission also found
`that the relevant claim of the ’655 patent is not invalid for
`lack of an adequate written description.
`Ajinomoto appeals the Commission’s claim construc-
`tion underlying the determination of no infringement by
`the earlier strains. CJ cross-appeals aspects of the deter-
`mination of infringement by the later strains and the rejec-
`tion of the invalidity challenge. We affirm.
`I
`A
`The ’655 patent claims E. coli bacteria that have been
`genetically engineered to increase their production of aro-
`matic L-amino acids, such as L-tryptophan, during fermen-
`tation, as well as methods of producing aromatic L-amino
`acids using such bacteria. See ’655 patent, col. 2, lines 40–
`45. In particular, the ’655 patent identifies a specific gene
`in the E. coli genome, the yddG gene, that encodes a mem-
`brane protein, the YddG protein. Id., col. 2, lines 46–48.
`That protein transports aromatic L-amino acids out of the
`bacterial cell and into the surrounding culture medium,
`where they can be collected. See id., col. 7, lines 11–16.
`When yddG gene activity in bacteria is enhanced so that
`more YddG protein is produced, the bacteria show in-
`creased production of, and increased resistance to, aro-
`matic L-amino acids. Id., col. 2, lines 49–57.1
`
`
`1 The specification defines a bacterium’s “resistance”
`to an amino acid as its ability “to grow on a minimal me-
`dium containing” the amino acid on “which unmodified or
`
`

`

`4
`
`AJINOMOTO CO., INC. v. ITC
`
`The ’655 patent describes three ways to enhance the
`activity of the yddG gene. First, plasmids containing addi-
`tional copies of the yddG gene can be introduced into the
`bacterium. Id., col. 2, lines 50–52; id., col. 5, line 62,
`through col. 6, line 2. Second, additional copies of the yddG
`gene can be inserted into the bacterial chromosome. Id.,
`col. 2, lines 52–54; id., col. 6, lines 3–6. Third, a stronger
`“promoter” than the one native to the E. coli yddG gene can
`be used. Id., col. 2, lines 54–57; id., col. 6, lines 12–15.2
`Claim 20, the only claim of the ’655 patent still asserted
`when the Commission issued its decision, claims “[a]
`method for producing an aromatic L-amino acid, which
`comprises cultivating the bacterium according to any
`one of claims 9–12, 13, 14, 15–18, or 19.” Id., col. 24, lines
`
`
`the wild type, or the parental strain of the bacterium can-
`not grow,” or its ability “to grow faster” on such a medium
`“than unmodified or the wild type, or the parental strain of
`the bacterium.” ’655 patent, col. 4, lines 49–56.
`2 A promoter is a nucleotide sequence within a DNA
`molecule, located adjacent to the nucleotide sequence that
`constitutes the gene to be expressed. The Lewin textbook
`cited by Ajinomoto shows a “typical promoter” around 41
`nucleotides long. J.A. 6043; see also J.A. 6177 (article by
`Deuschle et al., cited at ’655 patent, col. 6, lines 18–21,
`showing longer promoters). The promoter is the binding
`site for RNA polymerase, which initiates transcription (the
`first step in gene expression) by separating the two strands
`of DNA. The ’655 patent’s specification defines “[s]trength
`of promoter” with reference to the “frequency of acts of the
`RNA synthesis initiation.” ’655 patent, col. 6, lines 15–16.
`The promoter is only one part of a gene’s “expression
`regulation sequence,” which controls expression of the
`gene. See id., col. 3, line 14; id., col. 5, line 2. Besides pro-
`moters, the “expression regulation sequence” can include,
`e.g., operators, enhancers, terminators, and silencers.
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`5
`
`4–6 (emphasis added). Of the claims in that list, claims 9
`and 15 are the independent claims, and they are the two
`alternatives, under claim 20, of importance in this case.
`Claim 9 recites:
`9. A recombinant Escherichia coli bacterium,
`which has the ability to accumulate aromatic L-
`amino acid in a medium, wherein the aromatic L-
`amino acid production by said bacterium is en-
`hanced by enhancing activity of a protein in a cell
`of said bacterium beyond the levels observed in a
`wild-type of said bacterium,
`[1] and in which said protein consists of the
`amino acid sequence of SEQ ID NO: 2
`[2] and said protein has the activity to make
`the bacterium resistant to L-phenylalanine, fluoro-
`phenylalanine or 5[-]fluoro-DL-tryptophan,
`[3] wherein the activity of the protein is en-
`hanced by [3a] transformation of the bacterium
`with a DNA encoding the protein to express the
`protein in the bacterium, [3b] by replacing the na-
`tive promoter which precedes the DNA on the chro-
`mosome of the bacterium with a more potent
`promoter, [3c] or by introduction of multiple copies
`of the DNA encoding said protein into the chromo-
`some of said bacterium to express the protein in
`said bacterium.
`Id., col. 22, lines 51–67 (paragraph breaks and bold num-
`bering added). The Commission referred to limitation [1]
`as the “protein limitation,” limitation [2] as the “resistance
`limitation,” and limitation [3] as the “enhancement limita-
`tion.” Claim 15 is materially identical to claim 9, except for
`the protein limitation. Whereas claim 9 identifies the
`claimed protein by a specific amino-acid sequence, claim 15
`identifies it by reference to a corresponding DNA se-
`quence—a protein “encoded by the nucleotide sequence
`
`

`

`6
`
`AJINOMOTO CO., INC. v. ITC
`
`which hybridizes with the complement of the nucleotide se-
`quence of SEQ ID NO: 1 under” certain conditions. See id.,
`col. 23, lines 14–32.
`
`B
`In May 2016, Ajinomoto filed a complaint against CJ
`with the Commission under 19 U.S.C. § 1337. Ajinomoto
`alleged that CJ violated § 1337(a)(1)(B)(ii) by importing an-
`imal-feed-grade L-tryptophan products produced by a pro-
`cess covered by the ’655 patent.3 The Commission
`instituted an investigation based on Ajinomoto’s com-
`plaint.
`The parties before us, including the Commission, agree
`that whether the accused products were produced by a pro-
`cess covered by the patent is a question of infringement.
`The proceeding focused on three groups of E. coli strains
`that CJ has used to produce tryptophan. First, CJ’s “ear-
`lier strains” contained both the native E. coli yddG gene
`and the native E. coli yddG promoter, except that the first
`nucleotide of the promoter was changed through chemical
`mutagenesis, resulting in a stronger promoter. Second, in
`November 2016, several months after Ajinomoto filed its
`complaint, CJ began using its first “later strain,” which
`contained two copies of a yddG gene: (1) the native E. coli
`yddG gene with the native E. coli yddG promoter; and (2) a
`non-E. coli yddG gene with two promoters—(2a) a native
`non-E. coli yddG promoter and (2b) an rmf promoter.4
`Third, in December 2016, CJ started using its second “later
`
`
`3 Ajinomoto also alleged that CJ infringed U.S. Pa-
`tent No. 6,180,373, which similarly claims methods of pro-
`ducing tryptophan using genetically engineered bacteria.
`The ’373 patent expired on January 30, 2018, and is not at
`issue in this court.
`4 The rmf and rhtB promoters are promoters associ-
`ated with other genes in the E. coli genome.
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`7
`
`strain,” which also contained two copies of a yddG gene:
`(1) the native E. coli yddG gene with the native E. coli
`yddG promoter; and (2) a codon-randomized non-E. coli
`yddG gene with two promoters—(2a) an rmf promoter and
`(2b) an rhtB promoter.5
`In August 2017, the administrative law judge (ALJ) is-
`sued a final initial determination. The ALJ construed “re-
`placing the native promoter . . . with a more potent
`promoter” in the enhancement limitation to mean “remov-
`ing the native upstream region of the yddG gene and in-
`serting one of a class of promoters that controls expression
`of a different gene.” J.A. 90–91. Using that construction,
`the ALJ found that CJ’s earlier strains did not infringe; he
`found that they failed to meet the enhancement limitation
`because CJ created the more potent promoter in those
`strains by mutagenesis of a single nucleotide rather than
`removal of the entire native promoter and insertion of a
`new promoter. As to CJ’s later strains, the ALJ found that
`(a) the first later strain did not infringe because Ajinomoto
`had failed to prove that it met the resistance limitation,
`and (b) the second later strain also did not infringe because
`
`
`5 Each particular codon (three nucleotides in a row
`on a DNA molecule) that encodes for an amino acid always
`encodes for the same amino acid, but many of the 20 amino
`acids are encoded by more than one of the 64 codons. See
`Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1208 n.4
`(Fed. Cir. 1991) (discussing “redundancy” of genetic code).
`For instance, the DNA sequences TTA and TTG both code
`for the amino acid leucine. “Codon randomization” refers
`to creation of DNA molecules that use different codons (e.g.,
`TTA or TTG) to code for the same amino acid (e.g., leucine)
`in building the same protein. See Mycogen Plant Sci. v.
`Monsanto Co., 243 F.3d 1316, 1323 (Fed. Cir. 2001) (“[O]ne
`codon can be substituted for another in the gene without
`changing the amino acid and resulting protein.”).
`
`

`

`8
`
`AJINOMOTO CO., INC. v. ITC
`
`its non-E. coli YddG protein was not equivalent to the
`claimed E. coli YddG protein under the doctrine of equiva-
`lents. Finally, the ALJ found that claim 20 of the ’655 pa-
`tent is invalid for lack of an adequate written description
`of the “more potent promoter” limitation incorporated into
`that claim.
`In October 2017, the full Commission decided to review
`the ALJ’s final initial determination in its entirety, and in
`December 2017, the Commission issued its decision. It af-
`firmed the ALJ’s construction of “replacing the native pro-
`moter . . . with a more potent promoter” and accordingly
`affirmed the ALJ’s finding that CJ’s earlier strains did not
`infringe. But the Commission reversed several of the ALJ’s
`other findings. Specifically, it determined that both of CJ’s
`later strains met all disputed claim limitations and thus
`infringed claim 20 and that claim 20 was not proved to lack
`an adequate written description. The Commission accord-
`ingly entered a limited exclusion order against CJ’s infring-
`ing products, i.e., those made by both of CJ’s later strains
`but not its earlier strains. The Commission also issued a
`cease-and-desist order against CJ America, which held in-
`ventory of the infringing products.
`Ajinomoto and CJ both timely appealed. We have ju-
`risdiction under 28 U.S.C. § 1295(a)(6).
`II
`We begin with Ajinomoto’s appeal of the Commission’s
`finding of no
`infringement by the earlier strains.
`Ajinomoto challenges that finding solely by arguing that
`the Commission erred in its claim construction of “replac-
`ing the native promoter . . . with a more potent promoter.”
`Ajinomoto argues that, properly construed, the phrase is
`not limited to removing the entire native promoter and in-
`serting a new promoter, as the Commission concluded, but
`encompasses mutagenesis of individual nucleotides within
`the native promoter. We review the Commission’s claim
`construction de novo, as the Commission relied on only
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`9
`
`intrinsic evidence and made no factual findings based on
`extrinsic evidence. Teva Pharm. USA, Inc. v. Sandoz, Inc.,
`135 S. Ct. 831, 841 (2015); see Cont’l Circuits LLC v. Intel
`Corp., 915 F.3d 788, 795 (Fed. Cir. 2019). We agree with
`the Commission’s claim construction and therefore affirm
`the non-infringement finding.
`The ordinary and customary meaning of the claim lan-
`guage provides support for the Commission’s claim con-
`struction. The language of “replacing the native promoter
`. . . with a more potent promoter” suggests, in ordinary par-
`lance, an operation at the level of the entire promoter as a
`unit, not at the level of a single nucleotide that is just one
`small component of the promoter. To say that one is “re-
`placing” an object (e.g., a laptop computer, a bicycle, a sail-
`boat, a blender) suggests that one is doing more than
`altering one small part of it. That suggestion is bolstered
`when one also uses language (here, a “more potent pro-
`moter”) referring to the replacement at the level of the
`overall object. The suggestion is further reinforced by the
`most apt of the dictionary definitions of “replace” intro-
`duced before the Commission—“to provide a substitute
`for.” J.A. 10361; see also J.A. 5622 (patent applicants ex-
`plaining “replacing” as “substitut[ing]”). In many contexts,
`one would not refer to swapping out one small component
`of a larger unit as “replacing” the unit or as providing a
`“substitute” for the unit, even though the net result is a
`differently constituted larger unit. Context matters, of
`course, but here, Ajinomoto has not shown a contrary com-
`mon understanding (or even one of several common under-
`standings) among relevant artisans in the specific context
`of replacing a promoter with a more potent promoter. Ac-
`cordingly, the claim language, though hardly establishing
`a plain meaning, supports the Commission’s construction.
` The specification offers additional support, though it
`too is hardly plain insofar as it bears on the particular con-
`struction issue. The specification states that “the enhance-
`ment of gene expression can be achieved by locating the
`
`

`

`10
`
`AJINOMOTO CO., INC. v. ITC
`
`DNA of the present invention under control of more potent
`promoter instead of the native promoter.” ’655 patent,
`col. 6, lines 12–15. That statement speaks of a promoter as
`a unit, but it does not use the language of “replacing.” In-
`deed, the specification nowhere uses that language. But it
`does discuss “substituting” promoters, using a term that,
`as indicated above, is an apt definition of “replacing” here.
`The specification describes “[t]he present inventions” as in-
`cluding “[t]he bacterium according to the above bacterium,
`wherein native promoter of said DNA is substituted with
`more potent promoter.” Id., col. 3, lines 19–21. The term
`is then used in Example 4, which is titled “Substitution of
`the Native Upstream Region of yddG Gene by the Hybrid
`Regulatory Element Carrying the PL Promoter and SDlacZ
`in E. coli Chromosome,” and which involves removing the
`entire native promoter and inserting a new promoter. See
`id., col. 11, line 5, through col. 12, line 46. The sole specifi-
`cation example of “substitution” thus fits the Commission’s
`claim construction. And while the specification discusses
`mutagenesis, it does so only in the context of the protein-
`coding region of the yddG gene, not the promoter. See id.,
`col. 5, lines 18–30.
`We turn finally to the prosecution history—on which
`the parties to this case have focused most of their compet-
`ing analyses. We conclude that the best understanding of
`what transpired before the examiner further supports the
`Commission’s construction. Because the prosecution his-
`tory reinforces what is already suggested by the claim lan-
`guage and specification, this case provides no occasion,
`contrary to Ajinomoto’s contention (Ajinomoto Br. 34), for
`requiring clear and unmistakable disavowal or disclaimer
`to justify a claim construction contrary to a meaning evi-
`dent from the claim language and specification.
`What was claim 2 of the original application recited
`“[t]he bacterium according to claim 1, wherein said activi-
`ties of proteins . . . is enhanced by transformation of said
`bacterium with DNA coding for the protein . . . or by
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`11
`
`alteration of expression regulation sequence of said DNA on
`the chromosome of the bacterium.” J.A. 5047 (emphasis
`added).6 The examiner rejected the claim for lack of an ad-
`equate written description and lack of enablement. As to
`written description, the examiner explained that “[w]hile
`generic expression regulation sequences are known in the
`art, a particular, endogenous expression regulation se-
`quence for the DNA that encodes [amino-acid] SEQ ID
`NO:2, or related sequences, is not described.” J.A. 5371.
`“Without description of the endogenous regulation se-
`quence,” the examiner continued, “an endogenous regula-
`tion sequence that has been altered to increase expression
`of said protein also lacks adequate written description.” Id.
`Turning to enablement, the examiner stated:
`The specification, while being enabling for Esche-
`richia strains wherein the native promoter for the
`DNA encoding SEQ ID NO: 2 has been changed by
`substitution with a more potent promoter, does not
`reasonably provide enablement for the genus of an
`L-amino acid producing bacterium wherein the ac-
`tivity of proteins described by SEQ ID NO: 2 and
`related sequences is increased due to specific alter-
`ations within the chromosomal expression regula-
`tion sequence for DNA encoding said proteins.
`. . . .
`
`
`6 Although claims 9 and 15 issued from what were
`numbered as claims 12 and 24 when added during prose-
`cution, the parties do not dispute that the amendments to
`original claim 2 (which eventually was cancelled) are rele-
`vant to construing issued claims 9 and 15. The same “re-
`placing the native promoter . . . with a more potent
`promoter” language added to original claim 2 was eventu-
`ally added to claims 9 and 15.
`
`

`

`12
`
`AJINOMOTO CO., INC. v. ITC
`
`The instant specification teaches how to select
`Escherichia bacteria that have an increased pro-
`duction of L-amino acids, and the art teaches how
`to mutagenize chromosomal DNA and how to char-
`acterize the mutations in the DNA. However, nei-
`ther the specification nor the art contain any
`examples of how to specifically change endogenous
`Escherichia chromosomal expression regulation se-
`quences for the DNA encoding proteins described
`by SEQ ID NO: 2, or related sequences, such that
`the activity of said proteins in the bacteria is in-
`creased. The art and the specification provide en-
`ablement for inserting a known promoter in the
`chromosomal DNA to upregulate the expression of
`the DNA encoding SEQ ID NO: 2; however, neither
`the specification nor the art enable making specific
`changes to expression regulation sequences for
`DNA encoding SEQ ID NO:2 and related sequences
`on the chromosome of Escherichia bacteria. The
`art and specification lack a detailed description of
`the structure of the instant endogenous expression
`regulation sequences, and they lack any guidance
`on how to alter such sequences such that DNA ex-
`pression is increased; therefore, to make the in-
`stant bacteria with altered expression regulation
`sequences would be unpredictable.
`J.A. 5374–75.
`In response to the rejections, the applicants amended
`the claim to recite “replacing the native promoter that pre-
`cedes a DNA encoding said protein . . . with a more potent
`promoter” instead of “by alteration of expression regulation
`sequence of said DNA.” J.A. 5610. The applicants ex-
`plained the amendment as follows: “Applicants have
`amended Claim 2 consistent with the Examiner’s recogni-
`tion that the specification enables Escherichia strains
`wherein the native promoter for the DNA encoding SEQ ID
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`13
`
`NO: 2 has been changed by substitution with a more potent
`promoter.” J.A. 5622.
`Reading the written-description and enablement rejec-
`tions together, we think that the most reasonable under-
`standing of the examiner’s comments is that the examiner
`was drawing a distinction between alterations to the pro-
`moter, which were sufficiently described and enabled be-
`cause E. coli promoters were well understood in the art,
`and alterations to the expression-regulation sequence more
`broadly, which were not adequately described or enabled.
`To be sure, the examiner’s statement that the art and the
`specification “lack any guidance on how to alter such se-
`quences such that DNA expression is increased” might at
`first suggest that the applicants had not described and en-
`abled the full scope of “alteration.” But in context, this
`statement is best read as meaning that the applicants had
`not described and enabled the full scope of “expression reg-
`ulation sequence,” so that “alteration” of that sequence also
`was not adequately described or enabled, even though gen-
`eral techniques for altering DNA sequences were well
`known in the relevant art.
`We need not determine the precise basis for the exam-
`iner’s rejections, however, as “there is no principle of patent
`law that the scope of a surrender of subject matter during
`prosecution is limited to what is absolutely necessary to
`avoid a prior art reference that was the basis for an exam-
`iner's rejection.” Norian Corp. v. Stryker Corp., 432 F.3d
`1356, 1361 (Fed. Cir. 2005). Rather, patentees frequently
`“surrender more through amendment than may have been
`absolutely necessary to avoid particular prior art.” Id.
`That principle logically extends to amendments made to
`overcome rejections under § 112. Cf. Biogen Idec, Inc. v.
`GlaxoSmithKline LLC, 713 F.3d 1090, 1095–96 (Fed. Cir.
`2013). Indeed, we have stated more generally that “[t]he
`question is what a person of ordinary skill would under-
`stand the patentee to have disclaimed during prosecution,
`not what a person of ordinary skill would think the
`
`

`

`14
`
`AJINOMOTO CO., INC. v. ITC
`
`patentee needed to disclaim during prosecution.” Tech.
`Props. Ltd. LLC v. Huawei Techs. Co., 849 F.3d 1349, 1359
`(Fed. Cir. 2017). A patentee must “be held to what he de-
`clares during the prosecution of his patent,” because a con-
`trary rule would undermine “[t]he public notice function of
`a patent.” Springs Window Fashions LP v. Novo Indus.,
`L.P., 323 F.3d 989, 995 (Fed. Cir. 2003).
`We conclude that this is a case where the applicants
`surrendered more than may have been necessary. As dis-
`cussed above, the best reading of the prosecution history is
`that, to overcome the written-description and enablement
`rejections, it might well have sufficed if the applicants had
`narrowed their claims from alterations to the overall ex-
`pression-regulation sequence to alterations to the pro-
`moter. But the applicants did not merely change
`“expression regulation sequence” to “native promoter”;
`they also changed “alteration” to “replacing.” Just as
`“when different words are used in separate claims, they are
`presumed to have different meanings,” Aspex Eyewear, Inc.
`v. Marchon Eyewear, Inc., 672 F.3d 1335, 1349 (Fed. Cir.
`2012), when a word is changed during prosecution, the
`change tends to suggest that the new word differs in mean-
`ing in some way from the original word.
`That inference is bolstered by the applicants’ remarks
`accompanying the amendment. Those remarks effectively
`equate “replacing the native promoter . . . with a more po-
`tent promoter” in the amended claim with “chang[ing]” the
`native promoter “by substitution with a more potent pro-
`moter.” J.A. 5622. As we have already noted, Example 4,
`described as involving “substitution” of a promoter, in-
`volves removal of the entire native promoter and insertion
`of a new promoter. ’665 patent, col. 11, line 5, through col.
`12, line 46. The applicants’ remarks, understood in light of
`the word choices and the specification, thus reinforce the
`Commission’s conclusion that the new claim language does
`not include mutagenesis of individual nucleotides.
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`15
`
`For those reasons, we affirm the Commission’s claim
`construction and its finding that CJ’s earlier strains do not
`infringe based on that claim construction.
`III
`CJ, in its cross-appeal, challenges the Commission’s
`determinations that CJ’s second later strain met the pro-
`tein limitation, that both of CJ’s later strains met the re-
`sistance limitation, and that claim 20 is not invalid for lack
`of an adequate written description. We affirm the Commis-
`sion as to all three issues.
`A determination of infringement or non-infringement,
`whether literal or under the doctrine of equivalents, is a
`finding of fact, reviewed here for substantial evidence.
`Kinik Co. v. Int’l Trade Comm’n, 362 F.3d 1359, 1361 (Fed.
`Cir. 2004). But a determination of the applicability or in-
`applicability of prosecution history estoppel, which limits
`the availability of the doctrine of equivalents, is a matter
`of law, reviewed de novo. Spectrum Pharm., Inc. v. Sandoz
`Inc., 802 F.3d 1326, 1337 (Fed. Cir. 2015). The determina-
`tion that a patent claim did not lack adequate support in
`the written description is a factual finding, reviewed for
`substantial evidence. Rivera v. Int’l Trade Comm’n, 857
`F.3d 1315, 1319 (Fed. Cir. 2017). Ajinomoto had to prove
`infringement by a preponderance of the evidence, while CJ
`had to prove invalidity by clear and convincing evidence.
`See Motorola Mobility, LLC v. Int’l Trade Comm’n, 737
`F.3d 1345, 1348 (Fed. Cir. 2013); Enercon GmbH v. Int’l
`Trade Comm’n, 151 F.3d 1376, 1384 (Fed. Cir. 1998).
`A
`The Commission found that CJ’s second later strain in-
`fringed claim 20, which covers two alternatives of rele-
`vance in this case—the claim 9 alternative and the claim
`15 alternative. The infringement finding for CJ’s second
`later strain does not rest on the claim 15 alternative,
`which, in its protein limitation, requires a protein encoded
`
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`

`16
`
`AJINOMOTO CO., INC. v. ITC
`
`by a nucleotide sequence that hybridizes with the comple-
`ment of SEQ ID NO:1 (the nucleotide sequence of the E.
`coli yddG gene). The Commission did not find, and
`Ajinomoto does not argue for, either literal or equivalents
`infringement based on claim 15. The Commission found
`infringement under the claim 9 alternative—specifically, it
`found that the YddG protein encoded by the codon-random-
`ized non-E. coli yddG gene of this strain is an equivalent of
`SEQ ID NO:2 (the amino-acid sequence of the E. coli YddG
`protein), as required by the protein limitation of claim 9.
`CJ challenges that finding on two grounds. Based on
`an amendment to original claims made during prosecution,
`CJ asserts that prosecution history estoppel bars
`Ajinomoto from relying on the doctrine of equivalents to
`meet the protein limitation. Separately, CJ asserts that
`the non-E. coli YddG protein of CJ’s second later strain
`cannot reasonably be found to be an equivalent of the
`claimed E. coli YddG protein under the function-way-result
`test for equivalence. We address those arguments in turn.
`1
`Under the doctrine of prosecution history estoppel, “[a]
`patentee’s decision to narrow his claims through amend-
`ment may be presumed to be a general disclaimer of the
`territory between the original claim and the amended
`claim.” Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki
`Co., 535 U.S. 722, 740 (2002). The Supreme Court has
`specified three ways the patentee can rebut that presump-
`tion, each of which, if established, means that “the amend-
`ment cannot reasonably be viewed as surrendering a
`particular equivalent.” Id. First, “[t]he equivalent may
`have been unforeseeable at the time of the application.” Id.
`Second, “the rationale underlying the amendment may
`bear no more than a tangential relation to the equivalent
`in question.” Id. Third, “there may be some other reason
`suggesting that the patentee could not reasonably be
`
`

`

`AJINOMOTO CO., INC. v. ITC
`
`17
`
`expected to have described the insubstantial substitute in
`question.” Id. at 740–41.
`In this case, the relevant facts about what transpired
`during prosecution are as follows. Claim 1 as originally
`filed recited two alternative conditions for the claimed pro-
`tein:
`a protein as defined in the following (A) or (B) in a
`cell of said bacterium:
`(A) a protein which comprises the amino acid se-
`quence shown in SEQ ID NO:2 in Sequence listing;
`(B) a protein which comprises an amino acid se-
`quence including deletion, substitution, insertion
`or addition of one or several amino acids in the
`amino acid sequence shown in SEQ ID NO:2 in Se-
`quence listing.
`J.A. 5047. The examiner rejected that claim as anticipated
`by a reference disclosing the E. coli “yfiK gene product” (i.e.,
`the E. coli YfiK protein)—which differed from SEQ ID
`NO:2 by deletion, substitution, insertion, or addition of sev-
`eral amino acids and, therefore, did not come within the (A)
`alternative but did come within the (B) alternative. J.A.
`5378. In response, the applicants left the (A) alternative
`alone but replaced the language following (B) with new lan-
`guage: “a protein which comprises an amino acid sequence
`that is encoded by a nucleotide sequence that hybridizes
`with the nucleotide sequence of SEQ ID NO:1 under strin-
`gent conditions.” J.A. 5609.7
`
`
`7 As previously noted, claims 9 and 15 issued from
`new claims added at the same time as this amendment.
`See supra note 6. Claims 9 and 15 respectively contain the
`same language as the (A) and (B) limitations in claim 1 af-
`ter it was amended. Claim 20, the claim at issue, treats
`
`

`

`18
`
`AJINOMOTO CO., INC. v. ITC
`
`As an initial matter, CJ’s argument for prosecution his-
`tory estoppel in this case involves an unusual circum-
`stance. The infringement determination does not rest on
`finding an equivalent of the new claim language—namely,
`the (nucleotide) SEQ ID NO:1 language now in claim 15.
`Rather, it rests on finding an equivalent of the (amino-acid)
`SEQ ID NO:2 language now in claim 9, which was not itself
`altered by the amendment at issue. That is, the original
`claim provided two alternatives; only the second was mod-
`ified by amendment; and only the first is asserted as the
`basis for infringement by CJ’s second later strain. But we
`need not reach Ajinomoto’s contention that, in this circum-
`stance, prosecution history estoppel does not apply at all,
`i.e., that there is not even a presumed (though re