DCT

2:24-cv-06294

Pacira Pharma Inc v. eVenus Pharma Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:24-cv-06294, D.N.J., 09/09/2024
  • Venue Allegations: Venue is asserted based on Defendants' business operations and alleged infringing acts within New Jersey. Allegations include that eVenus is incorporated and has its principal place of business in New Jersey; Jiangsu Hengrui is a foreign company subject to suit in any district; and Fresenius Kabi has a regular and established place of business in the district.
  • Core Dispute: Plaintiff alleges that Defendants' Abbreviated New Drug Application (ANDA) to market a generic version of the anesthetic EXPAREL® infringes a patent on commercial-scale manufacturing processes for bupivacaine multivesicular liposomes.
  • Technical Context: The technology concerns large-scale manufacturing of extended-release local anesthetics, which encapsulate the drug bupivacaine in microscopic, multi-chambered lipid spheres to provide prolonged, non-opioid pain relief after surgery.
  • Key Procedural History: This lawsuit follows extensive, multi-year litigation between the same parties over three other patents in the same family, including a five-day bench trial on a related patent that concluded in February 2024. The complaint notes that during the prosecution of the patent-in-suit, Plaintiff submitted to the USPTO the expert reports and invalidity arguments that Defendants had raised in the prior litigation, which may strengthen the patent's presumption of validity against those same arguments.

Case Timeline

Date Event
2011-10-28 FDA approves New Drug Application (NDA) for EXPAREL®
2021-01-22 Earliest Priority Date for U.S. Patent No. 11,819,574
2021-11-08 Plaintiff files first Hatch-Waxman suit against Defendants ('495 patent)
2021-12-28 Plaintiff receives second Paragraph IV notice from eVenus ('495 & '336 patents)
2022-02-10 Plaintiff files second patent lawsuit against Defendants ('495 & '336 patents)
2022-08-30 U.S. Patent No. 11,426,348 ('348 patent) issues
2022-09-02 '348 patent listed in FDA Orange Book
2023-04-14 Plaintiff receives third Paragraph IV notice from eVenus ('348 patent)
2023-04-28 Plaintiff files third patent lawsuit against Defendants ('348 patent)
2023-11-21 U.S. Patent No. 11,819,574 issues
2023-12-06 '574 patent listed in FDA Orange Book
2024-02-06 Five-day bench trial begins concerning '495 patent
2024-03-11 Plaintiff receives fourth Paragraph IV notice from eVenus ('574 patent)
2024-09-09 Complaint filed in present action

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

  • Patent Identification: U.S. Patent No. 11,819,574, “Manufacturing of Bupivacaine Multivesicular Liposomes,” issued November 21, 2023.

The Invention Explained

  • Problem Addressed: The patent addresses the need for improved, large-scale manufacturing processes for bupivacaine multivesicular liposomes (MVLs) to meet growing market demand for non-opioid postsurgical analgesics (’574 Patent, col. 1:40-47). The complaint elaborates that scaling up production of these complex, inherently unstable MVL drug products was considered a significant, potentially "insurmountable" technical challenge (Compl. ¶¶8, 10).
  • The Patented Solution: The invention is a commercial-scale, multi-step process for preparing bupivacaine-encapsulated MVLs that results in a more stable final product (’574 Patent, Abstract; col. 3:39-44). The process involves a specific sequence of forming a water-in-oil emulsion, then a water-in-oil-in-water emulsion, followed by solvent removal and purification steps like microfiltration and diafiltration to produce large batches (e.g., 100-250 L) with specific, improved stability characteristics (Compl. ¶¶9, 11; ’574 Patent, col. 2:23-56).
  • Technical Importance: This scaled-up process enables a significant (up to 5-fold) increase in final product volume compared to prior methods while unexpectedly yielding a more stable formulation with less lipid degradation over time (Compl. ¶¶11, 60; ’574 Patent, col. 3:35-44).

Key Claims at a Glance

  • The complaint asserts independent product-by-process claim 1 and independent method of treatment claim 23.
  • Independent Claim 1: This claim is directed to "Batches comprising compositions of bupivacaine multivesicular liposomes (MVLs) prepared by a process," where the process includes the following essential steps and results in a product with the following properties:
    • (a) Mixing a first aqueous solution (phosphoric acid) with a solvent solution (containing bupivacaine and lipids) to form a first water-in-oil emulsion.
    • (b) Mixing the first emulsion with a second aqueous solution (containing lysine) to form a second water-in-oil-in-water emulsion.
    • (c) Removing the solvent to form a first aqueous suspension of MVLs.
    • (d) Reducing the volume by microfiltration to create a second aqueous suspension.
    • (e) Exchanging the supernatant with a saline solution via diafiltration to create a third aqueous suspension.
    • (f) Further reducing the volume by microfiltration to a final target bupivacaine concentration.
    • The resulting batch has a volume of about 100 L to 250 L.
    • The resulting composition has an average erucic acid concentration of about 105 µg/mL or less after six months of storage at 25° C.
  • Independent Claim 23: This claim is directed to "A method of treating or ameliorating pain in a subject in need thereof, comprising administering a composition of a batch of claim 1 to the subject."
  • The complaint also alleges infringement of dependent claims 2 and 24 and appears to reserve the right to assert other claims by alleging infringement of "at least" the specified claims (Compl. ¶¶62, 92).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' proposed generic versions of EXPAREL®, submitted to the FDA for approval in ANDA No. 214348 (Compl. ¶¶14, 65). The products are identified as bupivacaine liposome injectable suspensions in 133 mg/10 mL and 266 mg/20 mL (13.3 mg/mL) dosage forms (Compl. ¶14).

Functionality and Market Context

The accused products are injectable suspensions of microscopic, spherical particles called multivesicular liposomes (MVLs) that contain the anesthetic bupivacaine (Compl. ¶7). The complaint includes a cross-sectional diagram of an MVL particle from EXPAREL®, which it alleges the accused products replicate, illustrating how internal chambers release the drug over time (Compl. p. 5). The products are intended for post-surgical pain management to reduce or eliminate the need for opioids (Compl. ¶55). The complaint alleges, "on information and belief," that the manufacturing process used for the accused products will meet the specific steps and result in the specific composition properties recited in the asserted claims (Compl. ¶61).

IV. Analysis of Infringement Allegations

'574 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Batches comprising compositions of bupivacaine multivesicular liposomes (MVLs) prepared by a process, the process of preparing a batch comprising: (a)...(f) Defendants will manufacture their Proposed ANDA Products using a process that includes the first and second emulsification steps and subsequent purification steps (a)-(f). ¶61 col. 2:23-56
wherein each batch has a volume of about 100 L to about 250 L Defendants will manufacture their Proposed ANDA Products in batches with volumes between about 100 L and 250 L. ¶61 col. 17:1-5
wherein an average erucic acid concentration of at least three batches prepared by the process is about 105 µg/mL or less when measured after the compositions are stored at 25° C. for six months The batches of Defendants' Proposed ANDA Products will have an average erucic acid concentration of about 105 µg/mL or less when stored under the specified conditions. ¶61 col. 17:1-5
  • Identified Points of Contention:
    • Scope Questions: A central question will be the scope of the product-by-process claims. Infringement requires proof that the accused product is made by the claimed process. As the Defendants' manufacturing process is proprietary, a key dispute will be whether Plaintiff can obtain evidence from the ANDA and other discovery to demonstrate that the Defendants' process meets every limitation of the claimed process steps (a)-(f).
    • Technical Questions: The infringement analysis will turn on factual, data-driven comparisons. A primary question for the court will be whether the Defendants' product, as described in its ANDA stability data, actually demonstrates an "average erucic acid concentration of about 105 µg/mL or less" after six months of storage. The interpretation of the term "about" will be critical to this analysis.

V. Key Claim Terms for Construction

  • The Term: "an average erucic acid concentration of ... is about 105 µg/mL or less"

    • Context and Importance: This limitation is a crucial quantitative measure of the product's stability and is presented as a key patentable distinction over prior methods (Compl. ¶¶11-12). The dispute will hinge on whether Defendants' product meets this numerical threshold. Practitioners may focus on this term because the word "about" introduces ambiguity, and its construction will define the literal boundary of the claim.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of the word "about" itself suggests the patentee did not intend the claim to be limited to the precise value of 105 µg/mL. Plaintiff may argue it should be interpreted by a person of ordinary skill in the art to encompass a reasonable range of values consistent with the stability benefits described.
      • Evidence for a Narrower Interpretation: The patent provides specific data in its examples, such as an average concentration of 98.7 µg/mL for the new process batches (Table 1A, col. 20). A defendant could argue that "about 105 µg/mL" should be construed narrowly in light of these specific examples and the precision of the data presented.

  • The Term: "prepared by a process"

    • Context and Importance: For a product-by-process claim, the patentee must show that the accused product was made using the claimed method. The construction of the specific process steps, (a) through (f), will be critical to determining infringement, as any significant deviation in the accused process could support a non-infringement defense.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: Plaintiff may argue that the steps described in the specification (e.g., '574 Patent, col. 7:4-10:24) should be interpreted to cover equivalent steps that achieve the same function and result, even if not identical in every detail.
      • Evidence for a Narrower Interpretation: Defendant may argue for a narrow construction limited to the specific parameters and equipment disclosed in the patent's detailed description and examples, such as the specific mixing speeds and times ('574 Patent, col. 7:51-8:24).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement of method claims 23 and 24. The inducement theory is based on allegations that Defendants' proposed product labeling will instruct and encourage healthcare providers to administer the generic product for post-surgical pain relief, the patented method (Compl. ¶¶73, 93). The contributory infringement theory alleges the product is a material part of the invention, has been especially made for this infringing use, and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶74, 108).
  • Willful Infringement: The complaint does not use the term "willful," but it alleges facts to support such a claim. It asserts that Defendants had actual knowledge of the '574 patent, at the latest, from its listing in the FDA's Orange Book and from Plaintiff's service of the notice letter (Compl. ¶¶72, 88). This knowledge, combined with the extensive prior litigation history between the parties on closely related patents, is alleged as the basis for Defendants' knowledge of their infringing activities (Compl. ¶¶1-5).

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

  • A central issue will be one of factual correspondence: Can the plaintiff prove, through discovery of the confidential ANDA, that the defendants' proprietary manufacturing process contains every step of the process recited in claim 1 and that the resulting generic product will exhibit the specific, quantitative erucic acid stability marker required by the claim?
  • A key legal question will be one of definitional scope: How broadly will the court construe the term "about 105 µg/mL"? The interpretation of "about" could prove dispositive, as it directly controls the boundary for literal infringement of the patent's primary product-by-process claim.
  • An underlying strategic question will be the impact of the prosecution history: What legal weight will the court give to the fact that the plaintiff proactively submitted the defendants' prior invalidity arguments to the USPTO during the prosecution of the '574 patent? This raises the question of whether defendants may be estopped from re-litigating those same theories, potentially limiting their available defenses.