DCT

2:18-cv-03032

Fresenius Kabi USA LLC v. Bioq Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:18-cv-03032, D.N.J., 03/01/2018
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant has a regular and established place of business in the district, sought FDA approval to sell its product there, and collaborates with Sandoz Inc., which has a principal place of business in New Jersey.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of a New Drug Application (NDA) for a generic propofol injectable emulsion constitutes an act of infringement of a patent related to propofol formulations stored in containers with non-reactive closures.
  • Technical Context: The technology concerns pharmaceutical formulations of the widely used intravenous anesthetic propofol, specifically addressing challenges of microbial contamination and chemical degradation when using low-oil formulations.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act, triggered by Defendant’s submission of an NDA with a Paragraph IV certification. Subsequent to the filing of this complaint, an Inter Partes Review (IPR) proceeding (IPR2016-00254) resulted in the cancellation of numerous claims of the patent-in-suit, including independent claim 1. This post-filing event significantly narrows the scope of claims available for assertion in this litigation.

Case Timeline

Date Event
2003-07-10 ’010 Patent Priority Date
2013-07-02 ’010 Patent Issue Date
2015-11-25 IPR Filed Against ’010 Patent
2018-01-17 Defendant Sends Paragraph IV Notice Letter to Plaintiff
2018-03-01 Complaint Filing Date
2020-01-16 IPR Certificate Issued, Cancelling Claims of the ’010 Patent

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

  • Patent Identification: U.S. Patent No. 8,476,010, Propofol Formulations with Non-Reactive Container Closures, issued July 2, 2013. (Compl. ¶20).

The Invention Explained

  • Problem Addressed: The patent background describes that conventional propofol emulsions, which are oil-in-water formulations, pose two primary risks: (1) microbial contamination due to their high nutrient content (e.g., soybean oil) and (2) hyperlipidemia (high fat levels in the blood) in patients receiving long-term infusions due to the high fat content (’010 Patent, col. 2:5-19). While preservatives could be added, common agents like EDTA or sulfites introduce their own safety concerns (’010 Patent, col. 2:42-65).
  • The Patented Solution: The invention proposes a propofol formulation with a reduced oil/solvent content (less than 10% by weight) to mitigate the risks of microbial growth and hyperlipidemia (’010 Patent, col. 4:63-65). However, the inventors discovered that reducing the protective oil exposed the propofol to chemical degradation when stored in containers with standard closures, such as certain rubber stoppers (’010 Patent, col. 4:43-52). The patented solution is therefore a combination: a low-oil propofol formulation stored in a container that has an inert or non-reactive closure to prevent this degradation (’010 Patent, col. 4:48-58; Abstract).
  • Technical Importance: This approach sought to create a safer propofol product for long-term use by addressing the known drawbacks of high fat content and preservatives, while also solving the newly identified problem of container-closure incompatibility in low-oil formulations. (’010 Patent, col. 4:59-65).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’010 patent but does not specify which ones (Compl. ¶29). Following the IPR proceeding, surviving independent claims include Claims 33 and 57.
  • The essential elements of Independent Claim 33 are:
    • A sterile pharmaceutical composition of propofol in a container.
    • The container includes a closure and an oil-in-water emulsion.
    • The emulsion comprises an oil phase (with propofol and a solvent) and an aqueous phase.
    • The emulsion contains "from about 0 to about 10% by weight of the solvent."
    • The emulsion includes a "stabilizing layer" comprising "a surfactant and a protein."
    • When agitated under specific conditions, the formulation maintains at least 93% of its propofol concentration.
    • The closure is "selected from the group consisting of siliconized bromobutyl rubber, metal, and siliconized chlorobutyl rubber."
  • The complaint does not specify whether it will assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant BioQ’s proposed generic version of Diprivan®, identified as a "propofol injectable emulsion containing 10 mg propofol per 1 mL of emulsion formulation in a 50 mL single-use dispenser" (Compl. ¶25). This product is the subject of BioQ’s NDA No. 209809 (Compl. ¶26).

Functionality and Market Context

  • The product is an injectable anesthetic emulsion intended for sale in the United States upon receiving FDA approval (Compl. ¶25). The complaint alleges that BioQ will market the product through a collaboration with Sandoz Inc. (Compl. ¶8). The complaint does not provide specific technical details regarding the accused product's formulation (e.g., its solvent content) or its container closure system.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail to construct a claim chart. The infringement allegations are conclusory, stating only that the "use" and "commercial manufacture, use, offer for sale, sale, marketing, distribution, and/or importation" of BioQ's product "is covered by" or "would infringe" one or more claims of the ’010 Patent (Compl. ¶29-30). No facts are alleged that map specific features of the accused product to the limitations of any asserted claim.

No probative visual evidence provided in complaint.

  • Identified Points of Contention:
    • Evidentiary Question: A primary point of contention will be the specific composition of BioQ's product as detailed in its confidential NDA. To prove infringement of a surviving claim like Claim 33, the evidence must show that the product's formulation includes "from about 0 to about 10% by weight of the solvent" and a stabilizing layer with "a surfactant and a protein."
    • Technical Question: Does the container closure for BioQ's product meet the strict definition of the asserted claims? For Claim 33, infringement requires proof that the closure is specifically "siliconized bromobutyl rubber, metal, or siliconized chlorobutyl rubber." The complaint provides no information on this critical component.
    • Legal Question: Given the IPR history that invalidated many claims, a central dispute will be whether the accused product falls within the scope of the remaining, presumably narrower, claims. The Defendant may argue that its product was designed to avoid the specific limitations of the surviving claims.

V. Key Claim Terms for Construction

  • The Term: "a closure is selected from the group consisting of siliconized bromobutyl rubber, metal, and siliconized chlorobutyl rubber" (from Claim 33)

    • Context and Importance: This Markush group defines the exact type of container closure required. Practitioners may focus on this term because its narrow, "closed" language ("consisting of") makes it a potentially dispositive element for non-infringement. The patent's specification highlights that certain common rubber stoppers cause significant propofol degradation, whereas inert closures do not, making the choice of closure material critical to the invention (’010 Patent, col. 14, Table).
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party arguing for a broader scope (e.g., under the doctrine of equivalents) might point to more general language in the specification, such as the statement that a closure can be "coated with a suitable coating material to make it non-reactive or inert" (’010 Patent, col. 4:55-58), suggesting the inventive concept is "inertness" rather than only the three listed materials.
      • Evidence for a Narrower Interpretation: A party arguing for a narrow construction would emphasize that "consisting of" is a term of art that creates a strong presumption that the claim is limited to the listed elements. The patent’s detailed experimental data, which distinguishes between degrading and non-degrading stoppers, could be used to argue that the inventors deliberately chose this specific, limited list of materials for the claim (’010 Patent, col. 14, Table).

  • The Term: "from about 0 to about 10% by weight of the solvent" (from Claim 33)

    • Context and Importance: This term is crucial because it defines the low-solvent condition that necessitates the claimed inert closure. The dispute will likely center on the meaning of "about" and whether the accused product's solvent level falls within this range.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification indicates that the degradation problem was discovered in formulations with oil content "lower than about 10% (w/v)" and was not an issue in the prior art DIPRIVAN® product, which contained "10% (w/v) soybean oil" (’010 Patent, col. 4:60-65). This suggests the 10% mark is the critical boundary and "about" should provide some flexibility around it.
      • Evidence for a Narrower Interpretation: The patent’s own data shows a steep increase in propofol degradation as oil content falls below 10%; at 10% oil, recovery was 99.3%, while at 5% oil, it was only 82.9% (’010 Patent, col. 15, Table). A party could argue that a formulation at or very close to 10% does not experience the problem the patent claims to solve, and therefore "about 10%" should be construed narrowly to exclude such formulations.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, BioQ will induce infringement by directing or encouraging others (e.g., healthcare providers) to use the accused product in an infringing manner (Compl. ¶33). The basis for these allegations is BioQ’s stated intent to market and sell the product in the United States (Compl. ¶8, ¶13).
  • Willful Infringement: Willfulness is alleged based on BioQ's pre-suit knowledge of the ’010 Patent, as evidenced by its filing of a Paragraph IV certification and its notice letter to Fresenius (Compl. ¶27, ¶32). The complaint further alleges that BioQ acted "without a reasonable basis for believing that it would not be liable" for infringement (Compl. ¶35).

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

  • A core issue will be one of infringement in view of IPR: Following the cancellation of a significant portion of the patent’s claims, can the Plaintiff prove that the specific formulation and container closure of the Defendant's product, as described in its NDA, fall within the scope of one of the surviving, narrower claims? The IPR's outcome has fundamentally reshaped the landscape of this dispute.
  • A key evidentiary question will be one of technical and compositional identity: Does the Defendant's product actually contain "from about 0 to about 10% by weight of the solvent" and a stabilizing layer with "a surfactant and a protein," and is it stored in a container using one of the three specific closure materials required by Claim 33? The resolution of the case will likely depend on the undisclosed technical details within the Defendant’s NDA.