DCT

1:24-cv-00318

Wuhan Healthgen Biotechnology Corp v. Expresstec LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-00318, D. Del., 03/11/2024
  • Venue Allegations: Venue is asserted based on Defendants' incorporation in Delaware and their alleged commission of infringing acts and transaction of business within the district.
  • Core Dispute: Plaintiff alleges that Defendants' methods for manufacturing plant-derived recombinant human serum albumin (rHSA) infringe three U.S. patents covering specific techniques for extracting and purifying rHSA from transgenic rice.
  • Technical Context: The technology concerns "molecular pharming," which uses genetically engineered plants as bioreactors to produce high-purity proteins for therapeutic applications, presenting an alternative to sourcing proteins from human blood plasma.
  • Key Procedural History: The complaint alleges that Plaintiff provided Defendants with notice of the patents-in-suit on or about March 1, 2024, approximately ten days before filing the lawsuit.

Case Timeline

Date Event
2010-12-20 Priority Date for U.S. Patent No. 10,183,984
2010-12-24 Priority Date for U.S. Patent No. 9,951,100
2012-12-21 Priority Date for U.S. Patent No. 10,730,926
2018-04-24 U.S. Patent No. 9,951,100 Issues
2019-01-22 U.S. Patent No. 10,183,984 Issues
2020-08-04 U.S. Patent No. 10,730,926 Issues
2023-08-01 ExpressTec LLC allegedly acquires Ventria Bioscience Inc. (approx.)
2024-03-01 Plaintiff allegedly provides notice of patents to Defendant (approx.)
2024-03-11 Complaint Filed

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

U.S. Patent No. 9,951,100 - "Method for isolating and purifying recombinant human serum albumin from transgenic rice grain," issued April 24, 2018

The Invention Explained

  • Problem Addressed: The patent's background describes the technical difficulty and economic risk of developing a simple, cost-effective process to purify recombinant human serum albumin (rHSA) from transgenic rice grain, given the substantial impurities present (Compl. ¶25; ’100 Patent, col. 2:15-22).
  • The Patented Solution: The invention claims a specific, sequential three-step chromatography method to solve this problem. The process involves first using cation exchange chromatography, followed by anion exchange chromatography, and concluding with a hydrophobic chromatography step where the desired rHSA is collected in the non-adsorbed, "flow-through" fraction, which is claimed to result in a final product with over 99% purity (Compl. ¶25; ’100 Patent, Abstract & col. 2:50-68). The detailed description notes that this sequence is designed to first remove pigments and polysaccharides, then other proteins, before the final purification step (’100 Patent, col. 14:1-14).
  • Technical Importance: The claimed method provided a basis for an industrialized process to produce highly pure rHSA from a plant-based source, a key step in making such "molecular pharming" commercially viable as an alternative to using human plasma (Compl. ¶22; ’100 Patent, col. 2:35-43).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims, with independent claim 1 cited as representative (Compl. ¶¶ 26, 43).
  • Essential elements of independent claim 1 include:
    • A method for isolating and purifying rHSA from transgenic rice grain, sequentially comprising the steps of:
      1. subjecting a crude extract from the transgenic rice grain containing the rHSA to cation exchange chromatography to obtain primary product I;
      1. subjecting the primary product I to anion exchange chromatography to obtain secondary product II that contains the rHSA, wherein the secondary product II further comprises ammonium sulfate at a concentration from about 0.1 M to about 1 M;
      1. subjecting the secondary product II to hydrophobic chromatography, under a condition that the rHSA does not adsorb to the resins of the hydrophobic chromatography; and
      1. recovering non-adsorbed flow-through fractions from the hydrophobic chromatography to obtain the purified rHSA having a purity of more than about 99% rHSA monomer plus dimer and polymer by HPLC.

U.S. Patent No. 10,183,984 - "Method for extracting recombinant human serum albumin from transgenic rice grain," issued January 22, 2019

The Invention Explained

  • Problem Addressed: The patent identifies a need for a mature production process for extracting rHSA from transgenic rice, specifically one that improves the extraction efficiency of the target protein while simultaneously reducing the amount of unwanted, non-target proteins (Compl. ¶29; ’984 Patent, col. 2:17-24).
  • The Patented Solution: The invention discloses a method for the initial extraction of rHSA. The process involves grinding dehusked rice and mixing it with a specific "extraction buffer" containing a defined mixture of salts (phosphate, sodium acetate, ammonium sulfate, and sodium caprylate) at a specified pH range. This is followed by a step where the pH is lowered to precipitate non-target proteins, which are then filtered out, yielding a solution with a high concentration of rHSA (Compl. ¶29; ’984 Patent, col. 2:41-44). The specification explains that optimizing parameters like temperature and buffer composition enhances the extraction yield of rHSA (’984 Patent, col. 3:21-29).
  • Technical Importance: This patented method improves the quality of the initial crude extract by increasing the relative concentration of rHSA, thereby providing a more purified starting material for subsequent large-scale purification processes (Compl. ¶29; ’984 Patent, col. 4:5-27).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims, with independent claim 1 cited as representative (Compl. ¶¶ 30, 52).
  • Essential elements of independent claim 1 include:
    • A method for extracting rHSA from transgenic rice grain, comprising the steps of:
      1. removing the hull of transgenic paddy rice containing rHSA, and grinding the dehusked rice grain;
      1. mixing the transgenic milled rice grain with an extraction buffer and extracting with stirring to obtain mixture I, wherein the extraction buffer has a pH of between about 6.5 and 8, and comprises specified concentrations of phosphate, sodium acetate, ammonium sulfate, and sodium caprylate;
      1. adjusting pH of the mixture I to between about 4.0 and 4.5 and precipitating non-target proteins; and
      1. filtrating the mixture II and collecting the filtrate to obtain a solution containing a high concentration of rHSA.

U.S. Patent No. 10,730,926 - "Chromatographic method for isolating and purifying high-purity recombined human serum albumin," issued August 4, 2020

  • Technology Synopsis: This patent addresses the need for exceptionally high-purity rHSA (greater than 99.9999%) with extremely low levels of endotoxins for therapeutic applications (Compl. ¶33; ’926 Patent, col. 2:5-9). The patented solution is a sequential chromatographic method that involves using alcohol in specific buffer solutions during cation exchange chromatography to remove endotoxins and employing particular composite resins (e.g., cation/hydrophobic and anion/hydrophobic) to achieve the claimed purity levels (Compl. ¶33; ’926 Patent, Abstract & col. 2:25-36).
  • Asserted Claims: Independent claim 1 is asserted as representative (Compl. ¶34).
  • Accused Features: The complaint alleges that Defendants' methods for preparing their rHSA products, including Optibumin, result in a product with high purity and low endotoxin levels that falls within the scope of the patent rights (Compl. ¶¶ 40, 61).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the methods used by Defendants to manufacture, extract, and purify their line of rHSA products derived from rice grain, including the specifically named product "Optibumin" (Compl. ¶¶ 13, 36, 40).

Functionality and Market Context

  • The complaint alleges that Defendants' production process "harnesses the humble rice plant's natural ability" to manufacture proteins that become "concentrated within the rice-seed endosperm for easy harvest and purification" (Compl. ¶36). A copy of a webpage from Ventria's website describing this process is referenced as Exhibit 1 in the complaint (Compl. ¶36).
  • The resulting Optibumin product is marketed as the "highest purity albumin on the market" (Compl. ¶37). A copy of the product webpage from Ventria's website is referenced as Exhibit 7 (Compl. ¶37).
  • The complaint cites a Certificate of Analysis for Optibumin, referenced as Exhibit 8, which allegedly states the product has "100.0%" purity and an endotoxin level of "0.22 EU/mL" (Compl. ¶38).
  • A publication by an InVitria Vice President, referenced as Exhibit 9, is also cited for the proposition that Optibumin has "100% monomer purity" (Compl. ¶39). These allegations position the accused products as direct competitors operating in the same technical field and marketing similar high-purity characteristics.

IV. Analysis of Infringement Allegations

The complaint alleges infringement based on information and belief, stating that the specific methods used by Defendants cannot be reverse-engineered (Compl. ¶41). The infringement theory relies on public statements about the accused product's source (rice) and purity characteristics to infer that the manufacturing process must practice the claimed methods.

U.S. Patent No. 9,951,100 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for isolating and purifying recombinant human serum albumin (rHSA) from transgenic rice grain, sequentially comprising the steps of: 1) subjecting a crude extract...to cation exchange chromatography... Based on information and belief, Defendants use purification methods to prepare rHSA products derived from rice grain, which allegedly use the technologies claimed in the '100 patent. ¶40, ¶45 col. 13:50-55
2) subjecting the primary product I to anion exchange chromatography...wherein the secondary product II further comprises ammonium sulfate... Based on information and belief, Defendants' purification methods for their rice-derived rHSA products use the technologies claimed in the '100 patent. ¶40, ¶45 col. 13:56-62
3) subjecting the secondary product II to hydrophobic chromatography, under a condition that the rHSA does not adsorb to the resins of the hydrophobic chromatography... Based on information and belief, Defendants' purification methods for their rice-derived rHSA products use the technologies claimed in the '100 patent. ¶40, ¶45 col. 13:63-66
4) recovering non-adsorbed flow-through fractions...to obtain the purified...rHSA having a purity of more than about 99% rHSA monomer plus dimer and polymer by HPLC. Defendants market their Optibumin product as the "highest purity albumin on the market." A Certificate of Analysis allegedly states its purity is "100.0%," and a company publication allegedly states it has "100% monomer purity." ¶37, ¶38, ¶39 col. 14:1-4
  • Identified Points of Contention:
    • Evidentiary Question: The complaint is filed "on information and belief" and states the accused process cannot be reverse-engineered (Compl. ¶41). The central issue for the court will be what evidence is produced in discovery regarding the actual, step-by-step sequence of Defendants' purification process. The case will turn on whether that evidence shows the use of cation exchange, followed by anion exchange, followed by a hydrophobic chromatography step operating in a flow-through mode for rHSA.
    • Technical Question: A key technical question is whether Defendants' process, if it includes hydrophobic chromatography, operates "under a condition that the rHSA does not adsorb," as required by the claim. The precise operating parameters (e.g., buffers, salts) of Defendants' process will be critical to resolving this question.

U.S. Patent No. 10,183,984 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for extracting...rHSA from transgenic rice grain, comprising the steps of: 1) removing the hull...and grinding the dehusked rice grain; Defendants' rHSA products are allegedly "derived from rice grain" and manufactured from proteins "concentrated within the rice-seed endosperm." ¶36 col. 2:45-53
2) mixing the transgenic milled rice grain with an extraction buffer...wherein the extraction buffer has a pH of between about 6.5 and 8, and comprises [specified concentrations of four salts]; The complaint does not provide specific details about the chemical composition of the extraction buffer used by Defendants, but alleges on information and belief that the manufacturing process uses the patented technologies. ¶40, ¶54 col. 2:54 - 3:5
3) adjusting pH of the mixture I of step 2) to between about 4.0 and about 4.5 and precipitating non-target proteins...; The complaint does not provide details on any pH adjustment or precipitation steps used by Defendants, but alleges on information and belief that the manufacturing process uses the patented technologies. ¶40, ¶54 col. 3:30-44
4) filtrating the mixture II of step 3) and collecting the filtrate to obtain a solution containing high concentration of...rHSA. The complaint does not provide details on any filtration step, but alleges on information and belief that the manufacturing process uses the patented technologies. ¶40, ¶54 col. 3:45-56
  • Identified Points of Contention:
    • Evidentiary Question: The infringement theory for this patent is highly dependent on discovery. The central question is whether Defendants' process uses an extraction buffer with the specific combination of four salts within the concentration ranges and the pH range recited in claim 1, followed by the claimed pH-adjustment and precipitation step.
    • Scope Question: The construction of the term "about" as applied to the four salt concentrations and the pH range will be critical. The degree of flexibility this term affords the patentee will be a central question in determining the scope of the claim.

V. Key Claim Terms for Construction

For the '100 Patent:

  • The Term: "a condition that the rHSA does not adsorb to the resins of the hydrophobic chromatography" (from claim 1)
  • Context and Importance: This limitation defines the unique final purification step. Infringement will depend on whether Defendants' process, if it uses hydrophobic chromatography, is found to operate in this specific "flow-through" mode for the rHSA protein. Practitioners may focus on this term because it distinguishes the invention from typical "bind-and-elute" chromatography.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent's summary states the goal is to have the rHSA "not adsorb" so it can be recovered in the "non-adsorbed flow-through fractions" ('100 Patent, col. 2:61-64). This focus on the result, rather than the specific means, may support a broader functional interpretation.
    • Evidence for a Narrower Interpretation: The specification provides specific examples with particular salt concentrations (e.g., ammonium sulfate) to achieve the non-adsorption effect ('100 Patent, col. 15:32-38, col. 16:20-53). This may support an argument that the term is implicitly limited to the types of conditions disclosed.

For the '984 Patent:

  • The Term: "extraction buffer" (from claim 1)
  • Context and Importance: The claim explicitly defines the "extraction buffer" by reciting a pH range and required concentration ranges for four different chemical components. The entire infringement case for this patent hinges on whether Defendants' process uses a buffer that meets this multi-part definition.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of "about" before each numerical range suggests the patentee did not intend to be limited to the exact numbers. The specification's description of the invention as a "technology and process for high-efficiency extraction" may support a functional interpretation that covers buffers achieving the same enhanced result ('984 Patent, col. 2:22-24).
    • Evidence for a Narrower Interpretation: The patent attributes the improved extraction to a specific recipe, describing the buffer as comprising a particular list of components ('984 Patent, Abstract). The examples provide highly specific embodiments of the buffer composition, which could be used to argue that the claims should not be read to cover buffers with substantially different chemical makeups or concentrations outside the recited ranges (’984 Patent, Example 1).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. Inducement is based on allegations that Defendants actively encourage others (importers, sellers, users) to infringe, such as by promoting the use of the infringing products (Compl. ¶¶ 47, 56, 64). Contributory infringement is based on allegations that Defendants supply components (e.g., the Optibumin product itself) that are specially made for use in an infringing manner and are not staple articles of commerce (Compl. ¶¶ 48, 57, 65).
  • Willful Infringement: Willfulness allegations are based on alleged post-suit knowledge. The complaint asserts that Defendants have known of the patents-in-suit "at least as of March 1, 2024," and have nevertheless "proceeded to make, use, offer for sale, sell, and import the infringing products" with knowledge of infringement (Compl. ¶¶ 49, 58, 66).

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

The resolution of this dispute appears to depend on the answers to three central questions:

  1. A fundamental question will be one of evidence: As the complaint is filed on information and belief and acknowledges the accused methods are not public, the case will hinge on what discovery reveals about the proprietary chemical and procedural steps of Defendants' manufacturing process and whether those steps map onto the patent claims.
  2. A core legal issue will be one of definitional scope: How will the court construe key claim limitations, such as the requirement for a "condition that the rHSA does not adsorb" ('100 patent) and the precise chemical concentration ranges modified by "about" for the "extraction buffer" ('984 patent)? The outcome of claim construction will create the framework for the infringement analysis.
  3. An ultimate question may be one of technical comparison: Should discovery reveal a process that does not literally infringe, does Defendants' method for purifying rHSA from rice perform substantially the same function, in substantially the same way, to achieve the same high-purity result, raising a significant dispute under the doctrine of equivalents?