DCT

1:18-cv-10423

Glycosyn LLC v. Jennewein Biotechnologie GmbH

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-10423, D. Mass., 03/05/2018
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Massachusetts because Defendant conducts business in the Commonwealth, has sold or offered to sell infringing products in the District, and has purposefully directed sales and importation toward the District.
  • Core Dispute: Plaintiff alleges that Defendant’s process for manufacturing 2'-fucosyllactose Human Milk Oligosaccharide (2'-FL HMO) infringes a patent related to the biosynthesis of such oligosaccharides in engineered bacteria.
  • Technical Context: The case concerns the large-scale biotechnological production of Human Milk Oligosaccharides (HMOs), complex sugars found in human milk that are commercially significant as ingredients in infant nutrition products.
  • Key Procedural History: The complaint relies heavily on technical descriptions from Defendant's March 2015 "Generally Recognized as Safe" (GRAS) Notice No. 571, filed with the U.S. Food and D rug Administration, as evidence of the accused manufacturing process.

Case Timeline

Date Event
2011-02-16 ’230 Patent Priority Date
2014-07-30 Jennewein files U.S. trademark for “Mum’s Sweet Secret”
2015-03-01 Jennewein seeks FDA GRAS determination for its 2'-FL HMO
2015-09-08 Jennewein receives U.S. trademark registration for “Mum’s Sweet Secret”
2015-11-01 Jennewein receives FDA market approval for its 2'-FL HMO product
2016-06-01 Jennewein places 2'-FL HMO product into U.S. stream of commerce
2016-09-27 U.S. Patent No. 9,453,230 Issues
2018-03-05 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 9,453,230 - Biosynthesis of Human Milk Oligosaccharides in Engineered Bacteria

  • Patent Identification: U.S. Patent No. 9,453,230, issued September 27, 2016 (the “’230 Patent”).

The Invention Explained

  • Problem Addressed: The patent’s background section states that prior methods for producing Human Milk Oligosaccharides (HMOs), such as chemical synthesis, were limited by high costs, stereo-specificity issues, and product impurities, making inexpensive, large-scale manufacturing problematic (’230 Patent, col. 1:33-44).
  • The Patented Solution: The invention describes methods for engineering bacteria, such as E. coli, to efficiently produce fucosylated oligosaccharides. The solution involves a series of specific genetic modifications to the bacterium—for example, altering genes related to lactose metabolism and colanic acid synthesis—to create an optimized biological factory that can convert lactose into the desired HMO product (’230 Patent, Abstract; col. 1:45-56). Figure 3 of the patent illustrates a metabolic pathway engineered for 2'-FL production.
  • Technical Importance: This biotechnological approach provides an efficient and economical method for manufacturing large quantities of purified HMOs for commercial use in therapeutic or nutritional products (Compl. ¶3; ’230 Patent, col. 1:45-48).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claims 1 and 21 (Compl. ¶40).
  • Independent Claim 1 recites a method with the following essential elements:
    • Providing an E. coli bacterium with a deleted or inactivated endogenous β-galactosidase gene.
    • The bacterium contains a functional, promoter-less β-galactosidase gene inserted into an endogenous gene, resulting in a "low level" of activity between 0.05 and 200 units.
    • The bacterium contains an exogenous lactose-accepting fucosyltransferase gene.
    • The bacterium contains an inactivating mutation in a colanic acid synthesis gene.
    • The bacterium contains a functional lactose permease gene (E. coli lacY).
    • Culturing the bacterium in the presence of lactose.
    • Retrieving the resulting fucosylated oligosaccharide.
  • Independent Claim 21 recites a similar method, but specifies the inserted gene as a "functional exogenous wild-type β-galactosidase gene" and enumerates specific examples of colanic acid synthesis genes for the inactivating mutation, including E. coli wcaJ and wzxC.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the process used by Jennewein to manufacture its 2'-fucosyllactose Human Milk Oligosaccharide (2'-FL HMO) product, which is sold in the United States, including under the brand name "Mum's Sweet Secret" (Compl. ¶5, ¶22, ¶33).

Functionality and Market Context

The accused process is a fermentation method that uses a bioengineered, non-pathogenic strain of Escherichia coli BL21 (DE3) as a "processing aid" to produce 2'-FL HMO (Compl. ¶35). According to the complaint, which cites Jennewein’s regulatory filings, the bacterial cells are genetically modified to import lactose, enhance production of a precursor molecule (GDP-fucose), use a recombinant enzyme to synthesize 2'-FL from lactose, and export the final product into the surrounding medium for subsequent purification (Compl. ¶36). The resulting 2'-FL HMO is sold as a food ingredient for applications such as infant and toddler nutrition (Compl. ¶13-14).

IV. Analysis of Infringement Allegations

Allegations for the ’230 Patent

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
...providing an E. coli bacterium, said bacterium comprising a deletion or functional inactivation of an endogenous β-galactosidase gene... The accused process uses an E. coli strain in which the lacZ gene, which codes for β-galactosidase, is allegedly deleted or inactivated. A diagram from Defendant's GRAS notice, shown in the complaint, illustrates the lineage of the production strain. (Compl. ¶37). ¶43 col. 4:32-35
...a functional promoter-less β-galactosidase gene inserted into an endogenous gene such that the resultant bacterium comprises a low level of β-galactosidase activity, wherein said β-galactosidase activity comprises between 0.05 and 200 units... Defendant's GRAS Notice allegedly states that a "heat-inducible lacZ Ω gene fragment" was introduced into the production strain. The complaint alleges, on information and belief, that the resulting β-galactosidase activity is within the claimed range. ¶44 col. 7:22-30
...an exogenous lactose-accepting fucosyltransferase gene comprising an a(1,2) fucosyltransferase gene... The accused process allegedly uses a "heterologous 2-fucosyltransferase" encoded by an introduced wbgL gene to synthesize 2'-FL. A process diagram from the GRAS notice illustrates the function of this enzyme. (Compl. ¶38). ¶45 col. 3:22-29
...an inactivating mutation in a colanic acid synthesis gene... Defendant's GRAS Notice allegedly indicates that the wzxC and wcaJ genes are deleted in the production strain. The complaint asserts these are colanic acid synthesis genes. ¶46 col. 4:1-12
...a functional lactose permease gene, wherein said lactose permease gene comprises E. coli lacY... The accused process allegedly uses an E. coli strain containing a "deregulated version of the E. coli lacY gene" to import lactose from the medium. ¶47 col. 3:4-8
...culturing said bacterium in the presence of lactose... The cells in the accused process are allegedly "fed with the disaccharide lactose" as a precursor for 2'-FL synthesis. ¶48 col. 1:53-54
...retrieving a fucosylated oligosaccharide from said bacterium or from a culture supernatant... In the accused process, the final 2'-FL product is allegedly "purified from the medium by separation from the cells (biomass) by filtration." ¶49 col. 1:54-56

Identified Points of Contention

  • Factual Question: The complaint alleges "on information and belief" that the β-galactosidase activity in the accused process falls within the specific numerical range of "0.05 and 200 units." The case may raise a key factual question regarding what level of activity is actually produced by Jennewein's "heat-inducible" gene and how that activity is measured.
  • Scope Questions: A central aspect of the complaint is its reliance on Defendant's GRAS Notice to map the accused process to the patent's claims. A potential point of contention may be whether the technical descriptions made for a regulatory purpose correspond precisely to the specific limitations and definitions within the patent, which issued after the GRAS Notice was filed.

V. Key Claim Terms for Construction

  • The Term: "a low level of β-galactosidase activity... between 0.05 and 200 units"

  • Context and Importance: This quantitative limitation is central to the invention's strategy of maintaining an intracellular pool of lactose for synthesis while providing other functionalities. Practitioners may focus on this term because the complaint alleges it is met "on information and belief" (Compl. ¶44), suggesting it is not a direct admission from the Defendant's documents and will likely require discovery and expert testimony to resolve.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes the goal as producing "low, functional levels" of the enzyme, and the claim provides a numerically wide range, which could suggest that precision is not the main inventive concept (’230 Patent, col. 7:22-23).
    • Evidence for a Narrower Interpretation: The patent explicitly incorporates by reference a specific method for defining a "unit" of activity ("Miller JH, Laboratory CSH. Experiments in molecular genetics... 1972") (’230 Patent, col. 7:26-30). A party could argue that this reference strictly defines the required measurement protocol, potentially narrowing the application of the range.

  • The Term: "inactivating mutation in a colanic acid synthesis gene"

  • Context and Importance: This element is directed at increasing the intracellular pool of the GDP-fucose precursor by shutting down a competing metabolic pathway. The dispute will turn on whether the specific gene deletions alleged in the accused process (wzxC and wcaJ) fall within the scope of this term.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes the functional goal as eliminating the host's ability "to synthesize colanic acid," which could support construing the term to cover any mutation that achieves this result (’230 Patent, col. 4:2-4). The patent also provides deletion of the wcaJ gene as one example of such a mutation (’230 Patent, col. 4:11-12).
    • Evidence for a Narrower Interpretation: A party might argue that dependent claims or the specific list of genes in claim 21 (wcaJ, wzxC, wcaD, wza, wzb, or wzc) should inform the construction of the broader term in claim 1, potentially limiting its scope to the enumerated genes or those with very similar functions.

VI. Other Allegations

  • Indirect Infringement: The complaint makes a general allegation of inducing "customers and end users" (Compl. ¶40). However, the core of the infringement count is based on 35 U.S.C. § 271(g), which makes it an act of infringement to import, sell, or use within the U.S. a product which is made by a process patented in the U.S.
  • Willful Infringement: The complaint alleges willfulness based on Defendant having known or having had an objectively high likelihood of knowing its actions constituted infringement "by no later than the issue date of the '230 Patent, September 27, 2016," and continuing its activities nonetheless (Compl. ¶59-60).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A central evidentiary question will be one of quantitative measurement: does Jennewein's manufacturing process, as a matter of scientific fact, operate with a β-galactosidase activity level that falls within the specific numerical range of "0.05 and 200 units" as required by the asserted claims?
  • A core issue will be one of documentary interpretation: to what extent can the technical descriptions provided by Jennewein in its 2015 FDA GRAS Notice be used to establish, element by element, infringement of patent claims that issued more than a year later and contain specific limitations not necessarily addressed in the regulatory filing?