Jennewein Biotechnologie GmbH v. International Trade Commission (Fed. Cir. 2021)

By Kevin E. Noonan --

The International Trade Commission can more readily provide injunctive relief against an adjudged infringer than a district court, under appropriate conditions (i.e., with regard to an infringing product or a product made by infringing a claimed method).  In September, the Federal Circuit affirmed an exclusion order by the Commission in Jennewein Biotechnologie GmbH v. International Trade Commission (Glycosyn LLC joined as an Intervenor based on its patent being the basis for the exclusion order), based on importation of a product made by a patented method, which relied in part on an application of the doctrine of equivalents in establishing infringement (something that has become more common of late; see, e.g., Ajinomoto Co. v. International Trade Commission).

The matter arose when Glycosyn filed a complaint before the ITC under 19 U.S.C. § 1337 for importing milk oligosaccharaides (particularly, fucosyllactose or 2'-FL) made using methods claimed in its U.S. Patent No. 9,970,018.  Claim 1 is representative of the patented methods:

1.  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;
    (ii)  an exogenous functional β-galactosidase gene comprising a detectable level of β-galactosidase activity that is reduced compared to that of a wildtype 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.

Relevant limitations were that the bacterium has an inactivated colonic acid synthase gene and that the endogenous β-galactosidase gene (lacZ) is deleted or inactivated and an exogenous lacZ gene had been added to produce low-level ("between 0.05 and 200 Miller units") β-galactosidase activity; this enzymatic activity would degrade residual lactose that would be difficult and expensive to eliminate in the final product, while being expressed at a level low enough not to "significantly diminish the intracellular lactose pool."

Important cell characteristics resulting from these genetic manipulations included: (1) an increased intracellular guanosine diphosphate (GDP)-fucose pool; (2) an increased intracellular lactose pool; and (3) a fucosyltransferase, resulting in an apparently delicate metabolic balance.

The basis for Glycosyn's ITC complaint was Jennewein's importing 2'-FL made by the process claimed in the '018 patent.  Two of the strains express lacZα and lacZΩ, two gene fragments that when expressed together produce active β-galactosidase, with expression of the lacZΩ fragment being under temperature regulatory control (i.e., the gene is expressed at 42°C but not at 30°C).

The ALJ construed the limitations "'β-galactosidase activity comprises between 0.05 and 200 units' to mean 'β-galactosidase activity is measurable at between exactly 0.05 and exactly [200] Miller Units, as defined in Miller'"; "functional β-galactosidase gene" to mean "a functional sequence of DNA that encodes β-galactosidase;" and the term "exogenous" to have its plain and ordinary meaning.  The ALJ did not impose any temporal limits on the claimed activity ("the claimed activity need only be met 'at some point in time'").  Under this construction, the ALJ held that the two accused strains that expressed the lacZα and lacZΩ fragments infringed while a third strain (that only expressed the lacZα fragment) and did not use lactose to produce 2'-FL did not have sufficient evidentiary findings to adjudicate whether it infringed or not.

The Commission reviewed the ALJ's findings and concluded that the two strains that expressed lacZα and lacZΩ fragments infringed under the doctrine of equivalents, and that the third, lacZα-expressing strain did not infringe.  This appeal followed.

The Federal Circuit affirmed, in an opinion by Judge Chen joined by Judges Lourie and Bryson.  The panel expressly rejected Jennewain's three arguments:

(1) [that] Jennewein's [two strains adjudged to infringe did not] satisfy the claim limitation requiring that "the level of β-galactosidase activity comprises between 0.05 and 200 units"; (2) [that] Jennewein's [two strains adjudged to infringe did not] satisfy the "exogenous functional β-galactosidase gene" claim limitation; and (3) that the ITC erred in holding that "the level of β-galactosidase activity comprises between 0.05 and 200 units" claim limitation does not require the β-galactosidase activity to occur "within the claimed range at substantially all times during 2'-FL production and retrieval."

As for Jennewein's first argument, the Federal Circuit assessed the Commission's decision under the substantial evidence standard appropriate for questions of fact such as infringement.  The panel held that the evidence presented to the Commission was sufficient under this standard to withstand Jennewein's appeal, and in particular that no negative control strain was needed when performing the Miller assay to determine β-galactosidase activity.  There was no evidence of "background" lactose being produced in these cells or that any other enzymatic pathway produced this sugar other than the combination of the lacZα and lacZΩ fragments to produce functional (albeit barely) β-galactosidase (and thus that there was nothing to control for), according to the Court.  The panel agreed that any β-galactosidase activity detected at the lower temperature (30°C) was due to "leakage" in the temperature control of lacZΩ fragment expression, according to unrebutted expert (Glycosyn's)) testimony as well as other controls performed as part of the Miller assay.

The Court also was not convinced by Jennewein's quantitative arguments that showed the two negative control strains having higher Miller values than the accused strains.  Because the negative control strains should only have "background" β-galactosidase activity levels these results were anomalous for the panel, leading them to conclude that these strains were "not valid" as negative controls.  That the two control strains had different Miller levels also suggested to the Court that there was something amiss.  (There were also communications between Jennewein and a third party hired to assess infringement that undercut Jennenwein's arguments in this regard, to the effect that the control strains were "not suitable.")

The Federal Circuit found that Jennewein's strains satisfied the "exogenous functional β-galactosidase gene limitations" under the substantial evidence standard, at least under the doctrine of equivalents.  Jennewein based its arguments on the endogenous nature of the lacZα β-galactosidase gene fragment but the Federal Circuit agreed with the Commission (supported by substantial evidence) that the (barely) functional β-galactosidase gene was exogenous because the lacZΩ fragment was exogenous.  (The lacZΩ fragment itself is exogenous to the E. coli genome, having originated according to the opinion in a prophage.)

Finally, the panel agreed with the Commission that there was no temporal aspect recited in the claims and rejected Jennewein's argument that the Commission erred by not requiring Glycosan to establish that "the modified bacterium's level of β-galactosidase activity be 'within the claimed range substantially throughout 2'-FL production and retrieval'" based on the Commission's claim construction.  In reaching this conclusion, the Federal Circuit reviewed the Commission's claim construction de novo because the Commission had relied solely on intrinsic evidence, using the rubrics set forth in Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005) (en banc), finding no error.

Jennewein Biotechnologie GmbH v. International Trade Commission (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Bryson, and Chen
Opinion by Circuit Judge Chen

Comments

[Jim Demers]

"Wherein the level of β-galactosidase activity comprises between 0.05 and 200 units" is an odd construction. "Comprising" suggests that other levels of activity also fall within the scope of the claim.

[Kevin E Noonan]

Jim: Sometimes claims drafters use "comprising" as a catch-all modifier to indicate some level of "fuzziness" around ranges like this, but certainly (as you point out) there is a danger that the term can be used to find a variety of Section 112 issues depending on how the claims are construed. My understanding (without reviewing the specification or prosecution history) is that this level of activity is de minimis and yet effective in reducing the amount of lactose present in cells producing 2-FL. So any values outside this range would either be ineffective at reducing post-production lactose levels or would reduce the lactose pool in the cells during 2-FL production and thus reduce yield. In either case such embodiments would be disfavored economically and the patent holder might be content to let an infringer be saddled with such an inefficient production method.

Thanks for the comment