DCT

1:17-cv-11008

Janssen Biotech Inc v. Celltrion Healthcare Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-11008, D. Mass., 05/31/2017
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Massachusetts based on Defendant Celltrion Healthcare's office and business operations in Cambridge, its registration to do business in the state, and Defendants' failure to contest venue in prior related litigation.
  • Core Dispute: Plaintiff alleges that the cell culture media used by Defendants to manufacture a biosimilar version of Plaintiff's Remicade® biologic drug infringes a patent covering specific media compositions.
  • Technical Context: The dispute concerns chemically defined cell culture media, which are critical for the large-scale manufacturing of biologic drugs and are designed to eliminate risks of contamination from animal-derived components.
  • Key Procedural History: This complaint follows two earlier actions between the parties (a 2015 action and a 2016 action) concerning the same patent and biosimilar product. The complaint notes that a court in the prior consolidated actions ruled that Defendants had failed to comply with the BPCIA's pre-litigation procedures, and as a result, certain statutory limitations on remedies would not apply. This lawsuit was filed after Defendants allegedly attempted to restart the BPCIA's negotiation procedures post-ruling.

Case Timeline

Date Event
2003-12-03 Celltrion and HyClone enter non-disclosure agreement for cell culture media development.
2004-10-29 U.S. Patent No. 7,598,083 Priority Date.
2006-05-04 Patent application leading to the '083 patent is published.
2009-10-06 U.S. Patent No. 7,598,083 Issued.
2012-Q4 Defendants begin selling biosimilar infliximab in South Korea.
2014-08-08 Defendants submit abbreviated Biologic License Application (aBLA) for their biosimilar product.
2014-12-XX Janssen provides Defendants a list of patents, including the '083 patent, pursuant to BPCIA.
2015-03-06 Janssen files the "2015 action" against Defendants.
2016-04-05 FDA approves Defendants' biosimilar infliximab for sale in the U.S.
2016-Q4 Defendants begin selling biosimilar infliximab in the United States.
2017-05-31 Complaint filed.

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

U.S. Patent No. 7,598,083 - "Chemically Defined Media Compositions"

  • Issued: October 6, 2009

The Invention Explained

  • Problem Addressed: The patent background describes the risk of contaminating biopharmaceutical cell cultures with "adventitious particles" like viruses or prions when using media that contain animal-derived components, such as bovine serum ('083 Patent, col. 1:12-44). This contamination can pose a serious threat to patients receiving drugs made from these cultures and can limit production yields ('083 Patent, col. 1:19-24).
  • The Patented Solution: The invention provides a "chemically defined" cell culture medium, meaning it contains only known chemical compounds and is free of animal-derived proteins or other components ('083 Patent, col. 1:45-50). The formulation is designed to satisfy several critical criteria for biopharmaceutical production: it must support high viable cell densities, enable high titers of the desired protein (e.g., an antibody), and limit the production of metabolic waste like lactic acid ('083 Patent, col. 1:50-63). The patent discloses specific recipes comprising dozens of ingredients at defined concentration ranges to achieve these goals ('083 Patent, col. 9:50-11:3).
  • Technical Importance: By eliminating animal-derived components, the invention provides a safer and more consistent method for manufacturing biologic medicines, which was a significant step forward for the industry ('083 Patent, col. 1:45-50).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claim 2 (Compl. ¶74, 97, 112).
  • Independent Claim 1 recites:
    • A soluble composition, suitable for producing a final volume of cell culture media,
    • wherein the composition comprises a list of 61 specific components (e.g., anhydrous CaCl₂, FeSO₄·7H₂O, L-arginine.HCl),
    • with each component present in a specified concentration range (e.g., L-tryptophan from 2-500 mg/L).
  • The complaint notes that it reserves the right to assert additional claims (Compl. ¶115).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are at least two custom-made cell culture media used in the production of Defendants' biosimilar product: "Celltrion Growth Media" ("CGM") and "Celltrion Production Media" ("CPM") (Compl. ¶74).
  • Functionality and Market Context: These media are allegedly manufactured in the United States by HyClone Laboratories, Inc. at the direction and under the control of Defendant Celltrion (Compl. ¶7, 58, 75). They are used to grow the living cells that produce infliximab, the active biologic ingredient in Defendants' biosimilar product, which is marketed under the trade names Remsima and Inflectra as a biosimilar to Janssen's Remicade® (Compl. ¶2, 74, 113). The complaint alleges that these media are "critically important" to the manufacture of the biosimilar product approved for sale in the U.S. and worldwide (Compl. ¶83, 97).

IV. Analysis of Infringement Allegations

The complaint’s infringement theory relies entirely on the doctrine of equivalents, stating that for certain ingredients, the concentrations in the accused media are "insubstantially different from, and thus equivalent to, the ingredients at the claimed concentrations" (Compl. ¶59, 87).

'083 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
[A] soluble composition, suitable for producing a final volume of cell culture media, wherein the composition comprises the following components in the following amounts per liter of the final volume of cell culture media... The accused CGM and CPM are compositions used as cell culture media that contain all of the ingredients required by claim 1. ¶86 col. 9:50-11:3
[A list of 61 specified components, each with a claimed concentration range] Most of the required ingredients are alleged to be present in concentrations that are literally within the claimed ranges. The remaining ingredients are alleged to be present in concentrations "that are not substantially outside of the claimed ranges." ¶86 col. 9:50-11:3
The complaint alleges that the ingredients at these concentrations perform substantially the same function (e.g., promoting cell growth and antibody production), in substantially the same way, with substantially the same results as ingredients at the claimed concentrations, making the differences insubstantial. ¶87 col. 1:50-63
The complaint presents experimental data intended to show that the accused media exhibit "substantially similar performance" in cell culture compared to media meeting the literal claim limitations. This is supported by a graph showing comparable results for "Viable cell density" between the accused media and control media. ¶90, 91, 95 col. 1:55-58
  • Visual Evidence: The complaint provides a graph plotting "Viable cell density" over a period of seven days for multiple tested media formulations, which is used to argue that the accused media perform substantially similarly to media literally meeting the claim limitations (Compl. ¶91).
  • Identified Points of Contention:
    • Technical Questions: The core of the dispute will be factual and expert-driven. A key question is whether the experimental data presented in the complaint (Compl. ¶88-95) is sufficient to demonstrate that the concentration differences are insubstantial. The defense may challenge the methodology and conclusions of the experiments, which allegedly show that modifying the out-of-range ingredients to be within-range had "no substantial effect on the performance of the media" (Compl. ¶90).
    • Scope Questions: The case raises a classic doctrine of equivalents question: How far beyond the explicit numerical ranges recited in the claim can the patentee reach? The court will need to determine whether the differences in concentration between the accused media and the claimed ranges are truly "insubstantial" or if they represent a different, non-infringing formulation.

V. Key Claim Terms for Construction

  • The Term: The numerical concentration ranges for each of the 61 components (e.g., "L-tryptophan, 2-500 mg").
  • Context and Importance: The entire infringement case rests on the doctrine of equivalents, as the complaint concedes that some ingredient concentrations in the accused media fall outside the literally claimed ranges (Compl. ¶86). The interpretation of these numerical boundaries is therefore paramount. Practitioners may focus on whether the patent discloses the criticality of these specific ranges, which would impact the available scope under the doctrine of equivalents.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent claims very wide ranges for some components (e.g., "L-tryptophan, 2-500 mg"), which might suggest that the inventors did not consider the precise value within that range to be critical, potentially supporting an argument that values slightly outside the range are also equivalent ('083 Patent, col. 10:59). The specification does not appear to explicitly state that operation outside the claimed ranges is not possible.
    • Evidence for a Narrower Interpretation: A defendant would likely argue that the patentee defined the invention by meticulously listing 61 specific ingredients and their corresponding concentration ranges. By claiming these specific numerical boundaries, the patentee may have implicitly disclaimed compositions falling outside them. The sheer specificity of the claim language could be presented as evidence that these ranges are not suggestions but hard limits of the protected invention.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement against both Celltrion and Hospira. It claims Celltrion induced infringement by directing and controlling its agent, HyClone, to manufacture the infringing media in the U.S. (Compl. ¶122). It alleges Hospira induced infringement by entering into agreements with Celltrion to market and distribute the biosimilar product made using the infringing media (Compl. ¶135).
  • Willful Infringement: The complaint alleges willful infringement based on Defendants' knowledge of the '083 patent since at least December 2014, when Janssen identified it on a patent list as part of the BPCIA process (Compl. ¶98-99, 115). It further alleges knowledge based on the fact that HyClone, the manufacturer of the accused media for Celltrion, had previously received the confidential formulation for an embodiment of the '083 patent from Janssen's predecessor (Compl. ¶69, 100).

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

  • A core issue will be one of technical equivalence: Can Plaintiff’s experimental evidence persuade the court that the differences in ingredient concentrations between the accused media and the claimed formulation are "insubstantial"? This will likely devolve into a battle of experts over whether the accused media achieve the same result (e.g., cell viability and antibody titer) in the same way for the same function.
  • A key legal question will be the scope of the doctrine of equivalents: How will the court treat the dozens of specific numerical ranges in the claim? The case may turn on whether these ranges are interpreted as strict boundaries defining the invention or as exemplary embodiments that do not preclude finding equivalence for compositions lying just outside those boundaries.
  • A significant threshold issue involves liability for divided infringement: Can Janssen establish that Celltrion exerted sufficient "direction and control" over the U.S.-based manufacturer HyClone to be held directly liable for infringement, or will the infringement acts be attributed solely to HyClone, a non-party to this case?