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`PUBLIC VERSION
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`UNITED STATES INTERNATIONAL TRADE COMMISSION
`Washington, D.C.
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`In the Matter of
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`CERTAIN HUMAN MILK
`OLIGOSACCHARIDES AND METHODS
`OF PRODUCING THE SAME
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`Inv. No. 337-TA-1120
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`COMMISSION OPINION
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`The Commission has determined that there has been a violation of section 337 of the
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`Tariff Act of 1930, as amended, 19 U.S.C. § 1337 (“section 337”), on review of the final initial
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`determination (“FID”) of the presiding administrative law judge (“ALJ”), based on the
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`infringement of U.S. Patent No. 9,970,018 by respondent’s accused bacterial strains. The
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`Commission has also determined to reverse the FID’s decision declining to adjudicate
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`respondent’s alternative TTFL12 strain and finds no infringement as to that strain. This opinion
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`sets forth the Commission’s reasoning in support of that determination. In addition, the
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`Commission adopts the findings in the FID that are not inconsistent with this opinion.
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`I.
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`BACKGROUND
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`A.
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`Procedural Background
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`The Commission instituted this investigation on June 21, 2018, based on a complaint, as
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`amended and supplemented, filed by Glycosyn LLC (“Glycosyn”) of Waltham, Massachusetts.
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`See 83 Fed. Reg. 28865-66 (June 21, 2018). The complaint alleged violations of section 337
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`based upon the importation into the United States, the sale for importation, and the sale within
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`the United States after importation of certain human milk oligosaccharides, by reason of
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`infringement of certain claims of U.S. Patent Nos. 9,453,230 (“the ’230 patent”) and 9,970,018
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`(“the ’018 patent”). See id. The complaint also alleges the existence of a domestic industry.
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`1
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`The notice of investigation named Jennewein Biotechnologie GmbH of Rheinbreitbach,
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`PUBLIC VERSION
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`Germany (“Jennewein”) as respondent in this investigation. See id. The Office of Unfair
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`Import Investigations (“OUII”) is also a party to this investigation. See id.
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`The Commission later terminated the investigation as to all asserted claims of the ’230
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`patent and certain asserted claims of the ’018 patent based on the withdrawal of the allegations
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`pertaining to those claims. See Order No. 5 (Aug. 9, 2018), unreviewed, Comm’n Notice (Aug.
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`29, 2018); Order No. 15 (Oct. 30, 2018), unreviewed, Comm’n Notice (Nov. 29, 2018); Order
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`No. 17 (Nov. 19, 2018), unreviewed, Comm’n Notice (Dec. 12, 2018); Order No. 25 (Feb. 8,
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`2019), unreviewed, Comm’n Notice (Feb. 28, 2019). Claims 1-3, 5, 8, 10, 12, 18, and 23-28 of
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`the ’018 patent remain pending in this investigation.
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`The ALJ conducted an evidentiary hearing on May 14-17, 2019. On September 9, 2019,
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`the ALJ issued the FID finding a violation of section 337 based on the infringement of claims 1-
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`3, 5, 8, 10, 12, 18, and 24-28 (hereinafter, “the Asserted Claims”) but not claim 23 of the ’018
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`patent, based on non-infringement of that claim.1 See FID at 35. Furthermore, the FID finds
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`that the domestic industry requirement is satisfied.
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`The FID also contains a Recommended Determination (“RD”) recommending, should a
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`violation of section 337 be found, that the Commission issue a limited exclusion order (“LEO”)
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`barring entry of articles that infringe the Asserted Claims.2 The RD also recommends that the
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`Commission impose a bond in the amount of five (5) percent of the entered value of the
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`infringing articles during the period of Presidential review. Furthermore, as directed by the
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`1 Glycosyn did not petition for review of the FID’s finding that Jennewein does not infringe
`claim 23.
`2 Glycosyn did not request, and the RD does not recommend, a cease and desist order against
`Jennewein.
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`2
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`Commission (see 83 Fed. Reg. at 28865), the RD provides findings with respect to the public
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`PUBLIC VERSION
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`interest and recommends that the Commission determine that the public interest factors do not
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`preclude entry of the proposed LEO.
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`On September 23, 2019, Jennewein and the Commission’s Investigative Attorney (“IA”)
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`filed petitions for review of the FID.3 Jennewein petitioned for review of the FID’s findings
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`with respect to claim construction and infringement, and both Jennewein and the IA petitioned
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`for review of the FID’s decision not to adjudicate infringement with respect to Jennewein’s
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`TTFL12 bacterial strain, which Glycosyn did not accuse in its complaint. On October 1, 2019,
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`Glycosyn and the IA filed responses to the various petitions.4
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`On October 9 and 10, 2019, respectively, Glycosyn and Jennewein filed statements on the
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`public interest pursuant to Commission Rule 210.50(a)(4), 19 C.F.R. 210.50(a)(4).5 On October
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`23, 2019, non-party DuPont Nutrition & Health (“DuPont”) filed a public interest submission
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`pursuant to the Commission’s notice requesting public interest comments, see 84 Fed. Reg.
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`49335 (Sept. 19, 2019), supporting the ALJ’s recommended LEO and asserting that it has the
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`capacity to replace the excluded products in a commercially reasonable time.6
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`3 See Respondent Jennewein Biotechnologie GmbH’s Petition for Commission Review (Sep. 23,
`2019) (hereinafter, “Jennewein’s Pet.”); OUII Petition for Review (Sep. 23, 2019) (hereinafter,
`“IA’s Pet.”).
`4 See Complainant Glycosyn LLC’s Consolidated Response to Respondent Jennewein
`Biotechnologie GmbH’s and Office of Unfair Import Investigations’ Petitions for Commission
`Review (Oct. 1, 2019) (hereinafter, “Glycosyn’s Pet. Resp.”); Office of Unfair Import
`Investigations’ Response to Respondent’s Petition for Review (Oct. 1, 2019) (hereinafter, “IA’s
`Pet. Resp.”).
`5 See Complainant Glycosyn LLC’s Statement of Information Relating to the Public Interest
`(Oct. 9, 2019) (hereinafter, “Glycosyn’s PI Br.”); Public Interest Statement of Respondent
`Jennewein Biotechnologie GmbH (Oct. 10, 2019) (hereinafter, “Jennewein’s PI Br.”).
`6 See Public Interest Submission of DuPont Nutrition & Health (hereinafter, “DuPont PI Br.”).
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`PUBLIC VERSION
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`On January 30, 2020, the Commission issued a notice determining to review the FID in
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`part. See 85 Fed. Reg. 6573-75 (Feb. 5, 2020) (“the WTR/Remedy Notice”). Specifically, the
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`Commission determined to review: (1) the FID’s infringement findings with respect to
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`Jennewein’s bacterial strains adjudicated in this investigation; and (2) the FID’s decision not to
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`adjudicate infringement as to Jennewein’s alternative bacterial strain, i.e., the TTFL12 strain.
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`See id. The Commission determined not to review the remainder of the FID. See id. The
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`notice invited written submissions from the parties on issues under review, and from the parties,
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`interested government agencies, and any other interested parties on issues of remedy, the public
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`interest, and bonding. See id.
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`On February 18, 2020, the parties, including OUII, filed written submissions in response
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`to the WTR/Remedy Notice,7 and on February 25, 2020, the parties filed responses to each
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`other’s submissions.8 Also on February 18, 2020, non-party Abbott Laboratories (“Abbott”)
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`filed a written submission concerning the public interest in response to the WTR/Remedy Notice,
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`7 See Complainant Glycosyn LLC’s Response to Questions in the Commission’s Notice of
`Commission Decision to Review in Part a Final Initial Determination Finding a Violation of
`Section 337 (Feb. 18, 2020) (hereinafter, “Glycosyn’s Resp.”); Complainant Glycosyn LLC’s
`Initial Submission on the Form of Remedy, the Public Interest, and Bonding Pursuant to the
`Commission’s Notice of Commission Decision to Review in Part a Final Initial Determination
`Finding a Violation of Section 337 (Feb. 18, 2020) (hereinafter, “Glycosyn’s Remedy Br.”);
`Respondent Jennewein Biotechnologie GmbH’s Responses to Questions Raised by the
`Commission (Feb. 18, 2020) (hereinafter, “Jennewein’s Resp.”); Brief of the Office of Unfair
`Import Investigations on Issues under Review and on Remedy, the Public Interest, and Bonding
`(Feb. 18, 2020) (hereinafter, “IA’s Resp.”).
`8 See Complainant Glycosyn LLC’s Reply to Respondent’s and OUII’s Responses to the
`Commission’s Questions regarding Final Initial Determination Finding a Violation of Section
`337 (Feb. 25, 2020) (hereinafter, “Glycosyn’s Reply”); Respondent Jennewein Biotechnologie
`GmbH’s Reply to Responses by Glycosyn LLC and the Office of Unfair Import Investigations to
`Questions Raised by the Commission and Responses to Glycosyn’s and OUII’s Submissions on
`Remedy, the Public Interest, and Bonding (Feb. 25, 2020) (hereinafter, “Respondents’ Reply”);
`Reply Brief of the Office of Unfair Import Investigations on Issues under Review and on
`Remedy, the Public Interest, and Bonding (Feb. 25, 2020) (hereinafter, “IA’s Reply”).
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`and alleged that “Jennewein is the only supplier whose product has been fully qualified through
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`PUBLIC VERSION
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`Abbott’s quality and regulatory processes, raising public interest concerns from remedial
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`relief.”9
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`B.
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`The Asserted Patent
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`The ’018 patent issued on May 15, 2018. See JX-3, ’018 Patent. The ’018 patent, titled
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`“Biosynthesis of Human Milk Oligosaccharides in Engineered Bacteria,” relates to
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`“compositions and methods for producing fucosylated oligosaccharides” which are “typically
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`found in human milk” and which “serve critical roles in the establishment of a healthy gut
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`microbiome, in the prevention of disease and in immune function.” See id. at 1:27-39. The
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`specification of the ’018 patent states that “the invention . . . makes use of an engineered
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`bacterium E. coli or other bacteria engineered to produce” fucosylated oligosaccharides. See id.
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`at 15:66-16:4.
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`The ’018 patent specification explains that “[b]iosynthesis of fucosylated HMOS10
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`requires the generation of an enhanced cellular pool of both lactose and GDP11-fucose.” See id.
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`at 16:27-29; see also id. at Figure 3 (requiring both lactose and GDP-fucose for the synthesis of
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`2’-fucosyllactose). For example, the specification discloses that “[t]he ability of the E. coli host
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`strain to accumulate lactose was . . . engineered by simultaneous deletion of the endogenous
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`β-galactosidase gene (lacZ) and the lactose operon repressor gene (lacI)” while “the lacIq
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`promoter was placed immediately upstream of the lactose permease gene, lacY.” See id. at
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`16:37-43 (Example 1). The specification states that “[t]he modified strain thus maintains its
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`9 See Public Interest Submission of Abbott Laboratories (Feb. 18, 2020) (hereinafter “Abbott’s
`PI Br.”).
`10 “HMOS” refers to Human Milk Oligosaccharides.
`11 “GDP” refers to guanosine diphosphate. See JX-3, ’018 Patent at 1:61-63.
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`5
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`ability to transport lactose from the culture medium via LacY” but the lacZ (β-galactosidase)
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`PUBLIC VERSION
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`gene responsible for lactose catabolism (i.e., breakdown) is deleted. See id. at 16:43-47
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`(Example 1). Therefore, the specification continues, “[a]n intracellular lactose pool is . . .
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`created when the modified strain is cultured in the presence of exogenous lactose.” See id. at
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`16:47-49 (Example 1).
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`The specification also describes “bacterial host cells with the ability to accumulate a[n]
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`intracellular lactose pool while simultaneously possessing low, functional levels of cytoplasmic
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`β-galactosidase activity for example as provided by the introduction of a functional recombinant
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`E. coli lacZ gene or by a β-galactosidase gene from any of a number of other organisms.” See
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`id. at 7:22-28. The specification explains that “low level of cytoplasmic β-galactosidase activity
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`while not high enough to significantly diminish the intracellular lactose pool is nevertheless very
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`useful for tasks such as phenotypic marking of desirable genetic loci during construction of host
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`cell backgrounds, for detection of cell lysis due to undesired bacteriophage contaminations in
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`fermentation processes, or for the facile removal of undesired residual lactose at the end of
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`fermentations.” See id. at 7:37-45.
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`With regard to GDP-fucose production, the specification of the ’018 patent further states
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`that “[o]ne strategy for GDP-fucose production is to enhance the bacterial cell’s natural synthesis
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`capacity,” e.g., “by inactivating enzymes involved in GDP-fucose consumption, and/or by
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`overexpressing a positive regulator protein, RcsA, in the colanic acid (a fucose containing
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`exopolysaccharide) synthesis pathway.” See id. at 17:4-10. The specification explains that
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`“this metabolic engineering strategy redirects the flux of GDP-fucose destined for colanic acid
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`synthesis to oligosaccharide synthesis.” See id. at 17:10-12.
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`PUBLIC VERSION
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`Still further, the specification of the ’018 patent describes a “bacterium [that] possesses
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`fucosyl transferase activity,” e.g., “an exogenous fucosyltransferase gene.” See id. at 5:28-32.
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`The specification explains that “[a]n exemplary . . . fucosyltransferase gene is the wcfW gene”
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`and that “[p]rior to the present invention, this wcfW gene . . . was not suspected to possess the
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`ability to utilize lactose as an acceptor sugar,” i.e., as a substrate for HMOS synthesis. See id. at
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`5:28-38; see also id. at Figure 3 (involving α(1,2)FT, i.e., fucosyltransferase, in the synthesis of
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`2’-fucosyllactose).
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`Claim 1 of the ’018, from which the remaining asserted claims depend, patent recites the
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`following invention (with the disputed claim limitations in bold):
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`A method for producing a fucosylated oligosaccharide in a
`bacterium, comprising
`providing an isolated E. coli bacterium comprising,
`(i) a deletion or functional inactivation of an endogenous
`β-galactosidase gene;
`functional β-galactosidase gene
`(ii) an exogenous
`comprising a detectable level of β-galactosidase activity that
`is reduced compared to that of a wild-type E. coli bacterium,
`wherein the level of β-galactosidase activity comprises
`between 0.05 and 200 units;
`(iii) an inactivating mutation in a colanic acid synthesis
`gene; and
`(iv) an exogenous lactose-accepting fucosyltransferase gene;
`culturing said bacterium in the presence of lactose; and
`retrieving a fucosylated oligosaccharide from said bacterium or
`from a culture supernatant of said bacterium.
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`See id. at 111:41-57 (claim 1).
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`C.
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`Domestic Industry Product
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`The FID identifies Glycosyn’s E997 bacterial strain and its production of
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`2’-fucosyllactose (2’-FL) as practicing at least one claim of the ’018 patent. See FID at 7. The
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`FID also determines that Glycosyn satisfies the domestic industry requirement. See id. at 61-67,
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`7
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`96-113. No party petitioned for review of these findings, and the Commission determined not to
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`PUBLIC VERSION
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`review these findings.
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`D.
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`Accused and Redesigned or Alternative Products
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`The accused product in this investigation is Jennewein’s 2’-FL product which was
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`produced using E. coli bacterial strains #1540 and a derivative thereof, known as “the #1540
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`derivative” or “the #2410 strain” (collectively, “Accused Strains”). See FID at 7. The FID
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`finds that the Accused Strains infringe the Asserted Claims of the ’018 patent.
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`Jennewein also requested adjudication as to its redesigned or alternative TTFL12
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`bacterial strain in this investigation. Glycosyn did not accuse that strain in this investigation and
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`the FID declined to adjudicate infringement with respect to that strain. See id. at 28-35. The
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`Commission determined to review the FID’s decision not to adjudicate infringement with respect
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`to the TTFL12 strain. See 85 Fed. Reg. at 6574.
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`II.
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`LEGAL STANDARDS
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`A.
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`Standard on Review
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`Commission Rule 210.45(c) provides that “[o]n review, the Commission may affirm,
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`reverse, modify, set aside or remand for further proceedings, in whole or in part, the initial
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`determination of the administrative law judge” and that “[t]he Commission also may make any
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`findings or conclusions that in its judgment are proper based on the record in the proceeding.”
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`See 19 C.F.R. § 210.45(c). In addition, as explained in Certain Polyethylene Terephthalate
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`Yarn and Products Containing Same, “[o]nce the Commission determines to review an initial
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`determination, the Commission reviews the determination under a de novo standard.” Inv. No.
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`337-TA-457, Comm’n Op., 2002 WL 1349938, *5 (June 18, 2002) (citations omitted). This is
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`“consistent with the Administrative Procedure Act which provides that once an initial agency
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`decision is taken up for review, ‘the agency has all the powers which it would have in making
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`PUBLIC VERSION
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`the initial decision except as it may limit the issues on notice or by rule.’” Id. (citing 5 U.S.C.
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`§ 557(b)).
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`B.
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`Infringement
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`“An infringement analysis entails two steps. The first step is determining the meaning
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`and scope of the patent claims asserted to be infringed. The second step is comparing the
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`properly construed claims to the device accused of infringing.” Markman v. Westview
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`Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995) (en banc), aff’d, 517 U.S. 370 (1996)
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`(citations omitted). Infringement must be proven by a preponderance of the evidence. See
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`SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988). The
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`preponderance of the evidence standard “requires proving that infringement was more likely than
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`not to have occurred.” Warner-Lambert Co. v. Teva Pharm. USA, Inc., 418 F.3d 1326, 1341
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`n.15 (Fed. Cir. 2005).
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`Literal infringement requires the patentee to prove that the accused device contains each
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`and every limitation of the asserted claim(s). See Frank’s Casing Crew & Rental Tools, Inc. v.
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`Weatherford Int’l, Inc., 389 F.3d 1370, 1378 (Fed. Cir. 2004). Where literal infringement is not
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`found, infringement can still be found under the doctrine of equivalents. See TIP Sys., LLC v.
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`Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1376 (Fed. Cir. 2008) (“Infringement under the
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`doctrine of equivalents may be found when the accused device contains an ‘insubstantial’ change
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`from the claimed invention.”) (citations omitted).
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`III. DISCUSSION
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`The Commission determined to review: (1) the FID’s infringement findings with respect
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`to Jennewein’s bacterial strains adjudicated in this investigation; and (2) the FID’s decision not
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`9
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`to adjudicate infringement as to Jennewein’s alternative or redesigned bacterial strain, i.e., the
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`PUBLIC VERSION
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`TTFL12 strain. See 85 Fed. Reg. at 6574.
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`Infringement as to the Term Exogenous Functional β-Galactosidase Gene
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`A.
`The previously presiding ALJ12 construed “functional β-galactosidase gene” to mean
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`“functional sequence of DNA that encodes β-galactosidase.” See Order No. 22 at 29 (Dec. 18,
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`2018). No party petitioned for review of that construction. The parties also agreed that
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`“exogenous” is properly construed as “originating outside an organism, tissue, or cell.” See id.
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`at 12.
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`The FID finds that the Accused Strains do not literally satisfy the claim term “an
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`exogenous functional β-galactosidase gene,” but that the term is satisfied under the doctrine of
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`equivalents. See FID at 38-45. The FID reasons that Jennewein’s Accused Strains include two
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`distinct DNA sequences, namely, lacZα and lacZΩ, which, together, encode for the
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`β-galactosidase enzyme. See id. at 38-39. The FID concludes that “Jennewein’s Accused
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`Strains do not literally infringe ‘an exogenous functional β-galactosidase gene’ because they lack
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`a single sequence of DNA which functions to create a β-galactosidase gene.” See id. at 39.
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`Nevertheless, the FID finds “no difference between the combination of lacZα and lacZΩ genes
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`on the one hand, and any particular individual ‘functional β-galactosidase gene’ on the other.”
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`See id. at 40.
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`In addition, the FID recognizes that “lacZα in the Accused Strains was not added by
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`Jennewein, but was present in the original BL21 (DE3) strain which Jennewein engineered to
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`achieve the Accused Strains.” See id. at 44-45. The FID finds, however, that “the exogenous
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`12 At the time of Order No. 22, the investigation was assigned to the Chief ALJ. On April 2,
`2019, the investigation was transferred to Judge Elliot.
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`nature of lacZΩ is enough to meet the limitation” at issue. Id. The FID explains that “[i]t is the
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`PUBLIC VERSION
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`combination of lacZα and lacZΩ which is equivalent to the claimed ‘β-galactosidase gene,’ and
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`this combination does not exist until lacZΩ is inserted into the bacterium’s genome from outside
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`the organism.” See id. at 45. Thus, the FID concludes, “the combination is ‘exogenous’ and
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`satisfies the claim limitation at least under the doctrine of equivalents.” See id.
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`Jennewein petitioned for review of the FID’s infringement findings with respect to the
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`claim term “an exogenous functional β-galactosidase gene.” Jennewein’s Pet. at 30-35.
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`Jennewein did not dispute the FID’s findings that the combination of the lacZα and lacZΩ genes
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`is equivalent to a functional β-galactosidase gene, but Jennewein argued that the combination is
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`not exogenous because only lacZΩ is exogenous while lacZα is endogenous.13 See id. at 31.
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`Jennewein reasoned that the FID “departs from the parties’ agreed-upon construction for
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`‘exogenous’” and “incorrectly concludes that ‘[i]t is the combination of lacZα and lacZΩ which
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`is equivalent to the claimed ‘β-galactosidase gene,’ and this combination does not exist until
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`lacZΩ is inserted into the bacterium’s genome from outside the organism.’” See id. (citation
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`omitted) (emphasis in original). Jennewein explained that “[t]he claim language does not
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`encompass a combination of gene fragments that did not ‘exist’ until one fragment is inserted
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`into the genome” but “[r]ather, it requires that the combination itself originated outside of
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`Jennewein’s strain.” See id. (citation omitted).
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`The Commission finds that the FID correctly determined that Jennewein’s Accused
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`Strains include a combination that is equivalent to the claimed “exogenous functional
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`β-galactosidase gene.” See FID at 38-45. Jennewein argued that the ID’s finding that the
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`13 Jennewein explains that “‘endogenous’ genes are those present in the host strain prior to any
`genetic engineering.” Jennewein’s Pet. at 34 (citing Hr’g Tr. (Prather) at 441:25-442:4).
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`11
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`combination “does not exist” in the host strain until lacZΩ is inserted into the bacterium’s
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`PUBLIC VERSION
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`genome, is incorrect because, in Jennewein’s view, the construction of “exogenous” (i.e.,
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`“originating outside an organism, tissue, or cell”) requires that “the combination itself
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`originate[s] outside of Jennewein’s strain.” See Jennewein Pet. at 31. This alleged distinction,
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`however, is unpersuasive. Indeed, as the FID finds, the combination does not exist in the
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`original strain, and therefore the combination itself does not originate from within the organism.
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`See FID at 44-45 (citing CX-213 at Figure 2, 5158). Thus, the Commission agrees with the FID
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`that “the exogenous nature of lacZΩ is enough” to make the combination exogenous and any
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`difference between the claim term “an exogenous functional β-galactosidase gene” and the
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`accused products is insubstantial. See id. at 45; accord Glycosyn’s Pet. Resp. at 28; IA’s Pet.
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`Resp. at 10.
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`In addition, the Commission finds that lacZα, which is present in the genetically-
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`engineered strain, i.e., BL21[DE3], is also exogenous as compared to the wild-type E. coli
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`bacterium. See Glycosyn’s Pet. Resp. at 30-31. As Glycosyn explains, “[i]t is . . . undisputed
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`that the lacZα gene exists in the BL21(DE3) genome only by way of human intervention.” See
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`id. at 30 (citing CX-213 (Jennewein’s GRAS Notice) at CX-213.297 (“Since its isolation in
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`1818, the E. coli B strain has also undergone multiple rounds of genetic manipulation resulting in
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`the strain BL21 (DE3).”); RX-386C (Parschat14) at Q/As 68-69). In addition, “it is undisputed
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`that the DE3 is derived from a prophage, or in other words, a virus, that infects E. coli. to insert
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`foreign DNA into the E. coli.” See id. at 31 (citing RX-386C (Parschat) at Q/As 133-134 (“We
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`discovered there was actually a lacZ[α] like fragment already present in the DE3 prophage in the
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`14 Katja Parschat is Jennewein’s Deputy Head of Research and Development.
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`12
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`genome of strain #1540. . . . A prophage is the genome [of] an E. coli virus or phage or part of
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`PUBLIC VERSION
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`that genome that is integrated into the bacterial chromosome replicate.”)).
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`The language of the Asserted Claims and the specification of the ’018 patent make clear
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`that the claimed genetically-engineered bacterium and its “exogenous functional β-galactosidase
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`gene” are to be compared to the native or wild-type E. coli bacterium rather than to a genetically-
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`engineered strain, i.e., BL21[DE3]. See JX-3, ’018 patent at 111:45-49 (claim 1) (“A method
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`for producing a fucosylated oligosaccharide in a bacterium comprising[:] providing an isolated
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`E. coli bacterium comprising . . . an exogenous functional β-galactosidase gene comprising a
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`detectable level of β-galactosidase activity that is reduced compared to that of a wild-type E. coli
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`bacterium.”) (emphasis added); id. at 5:1-5 (“The bacteria used herein to produce HMOS are
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`genetically engineered to comprise an increased intracellular guanosine diphosphate (GDP)-
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`fucose pool, an increased intracellular lactose pool (as compared to wild type) and to comprise
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`fucosyl transferase activity.”) (emphasis added); id. at 6:45-53 (“In the case of lactose and GDP-
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`fucose, endogenous E. coli metabolic pathways and genes are manipulated in ways that result in
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`the generation of increased cytoplasmic concentrations of lactose and/or GDP-fucose, as
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`compared to levels found in wild type E. coli. For example the bacteria contain at least 10%,
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`20%, 50%, 2x, 5x, 10x or more of the levels in a corresponding wild type bacteria that lacks the
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`genetic modifications described above.”) (emphasis added).
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`There is no dispute that, as compared to the wild-type E. coli bacterium, both lacZα and
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`lacZΩ are exogenous, i.e., they “originat[e] outside an organism, tissue, or cell.” See CX-213 at
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`CX-213.297; RX-386C (Parschat) at Q/As 68-69, 133-34. Thus, the Commission has
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`determined to affirm with modification the FID’s finding that the Accused Strains infringe the
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`Asserted Claims under the doctrine of equivalents, and supplements the FID’s analysis as
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`discussed above.
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`B.
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`Adjudication of Infringement with Respect to the TTFL12 Strain
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`During the investigation, Jennewein sought adjudication of infringement with respect to its
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`TTFL12 bacterial strain, which Glycosyn did not accuse in its complaint. Jennewein identified
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`the TTFL12 strain on September 14, 2018, in its Ground Rule 7.2 disclosure15 (CX-226C) and in
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`its interrogatory responses served on November 5, 2018 (CX-237C). Jennewein further
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`provided two documents, RX-320C (a draft article) and RX-382 (European Patent Application
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`No. 14 162 869.3) (both produced on August 21, 2018), to establish the relevant features of the
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`TTFL12 strain.
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`The FID declines Jennewein’s request for adjudication, reasoning that “there can be no
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`dispute that Glycosyn has not accused [the TTFL12 strain] of infringement.” See FID at 28.
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`The FID states that Commission precedent follows “a four-factor test as to whether a respondent
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`has met its burden to show that infringement of a redesigned product should be adjudicated,”
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`namely, whether “[t]he product [is]: (1) within the scope of the investigation, (2) imported,
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`(3) sufficiently fixed in design, and (4) subject to extensive discovery.” See id. at 29 (citing
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`Certain Two-Way Radio Equipment and Systems, Related Software, & Components Thereof, Inv.
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`No. 337-TA-1053, Comm’n Op. at 8, 2018 WL 8648379 (Dec. 18, 2018) (“Two-Way Radio”)).
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`“Of these factors, [the FID] finds Respondents have not met their burden as to the fourth
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`factor, subject to extensive discovery.” See id. Specifically, the FID determines that
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`Jennewein failed to “provide[] ‘extensive’ or ‘sufficient’ discovery on the TTFL12 strain.” See
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`15 Ground Rule 7.2 relates to the “Disclosure of Products Within the Scope of the [Notice of
`Investigation].” See Order No. 2 (June 21, 2018).
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`id. at 32. The FID reasons that “while Jennewein identified TTFL12 as falling under the scope
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`of the investigation in its Ground Rule 7.2 disclosure [(CX-226C)], and identified the ‘draft’
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`article, RX-0320C, as evidence of TTFL12’s relevant features, it did not identify the patent
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`application [(RX-382)] such that Glycosyn would have been on notice of it,” because the patent
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`application “does not refer to TTFL12 by name.” See id. at 32-33. The FID further finds that
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`“RX-0320C may provide information on the conception of TTFL12, but it does not sufficiently
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`identify and describe a product that could serve as an accused product.” See id. at 34.
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`The FID also rejects Jennewein’s discovery responses as insufficient because they were
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`served on the last day of discovery, which ended on November 5, 2018. See id. The FID
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`determines that Jennewein’s failure to identify TTFL12 in response to Glycosyn’s request for
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`admission on importation “was more than enough to dissuade Glycosyn from investigating
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`anything other than the #1540 strain during discovery.” See id. at 34-35. The FID further finds
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`that “Glycosyn [was] on notice of just three things: a strain referred to as TTFL12 exists and
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`was described in an unpublished, undated article as lacking a lacZ gene (CX-0226; CX-0320C);
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`at some point the strain was used to create an unspecified amount of 2’-FL (CX-2037C at 1-2);
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`but that 2’-FL had not been imported into the United States (CX-0216C at 5).” See id. at 34.
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`The FID recognizes that “Glycosyn failed to take discovery of its own on [the TTFL12]
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`issue . . . and to respond to Jennewein’s own requests for admission on TTFL12,” but the FID
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`finds that “it is Jennewein’s burden to introduce TTFL12-based 2’-FL into the case.” See id. at
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`35 (citing Two-Way Radio). Thus, the FID concludes that “adjudication of whether the TTFL12
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`strain infringes [is not] appropriate at this time because the discovery on TTFL12 was not
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`adequate.” See id.
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`Jennewein and the IA petitioned for review of the FID’s alleged failure to adjudicate
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`infringement with respect to Jennewein’s TTFL12 bacterial strain. Jennewein’s Pet. at 35-41;
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`IA’s Pet. at 5-22. Jennewein argued that the FID errs in requiring a heightened burden of
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`“extensive discovery” where Commission precedent requires only that the respondent “provid[e]
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`sufficient information to put the complainant on notice that [the TTFL12 strain] may be at issue.”
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`See Jennewein’s Pet. at 37-38 (citing Certain Television Sets, Television Receivers, Television
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`Tuners, & Components Thereof, Inv. No. 337-TA-910, Order No. 46 at 23 (Nov. 28, 2014),
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`unreviewed, Comm’n Notice (Dec. 3, 2014)); accord IA’s Pet. at 22 (“[T]he [FID’s] conclusion
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`that the disclosure was somehow not ‘sufficient’ was a clearly erroneous finding of material fact
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`that merits review by the Commission.”).
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`Jennewein also argued that the FID should have adjudicated non-infringement because
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`the “TTFL12 strain lacks a functional β-galactosidase gene, and therefore it is incapable of
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`having any β-galactosidase activity as the claim clearly requires.” See Jennewein’s Pet. at 39.
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`Jennewein asserted that “[its] witnesses explained the structure and capabilities of the TTFL12
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`strain such that a noninfringement opinion would be straightforward.” See id. at 39-40 (citing
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`RX-320C (Jennewein draft manuscript produced August 2018) (“[g]enes encoding proteins
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`involved in pathways that compete with 2’-FL biosynthesis were inactivated or deleted”); RX-
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`409C (Stephanopoulos16 RWS17) at Q/A 278 (testifying that the lacZ gene has been deleted or
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`inactivated and that TTFL12 was not further engineered to insert a functional exogenous
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`β-galactosidase gene); Hr’g Tr. (Parschat) at 384:10-17 (“The complete lacZ gene as occurs in
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`16 Gregory Stephanopoulos was Jennewein’s technical expert in this investigation.
`17 “RWS” refers to Rebuttal Witness Statement.
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`16
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`the operon is not present in the TTFL-12 strain.”); RX-387C (Parkot18 Witness Statement
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`(“WS”)) at Q/A 85 (“The TTFL12 strain is a