DCT

2:23-cv-02367

Pacira Pharma Inc v. eVenus Pharma Laboratories Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-02367, D.N.J., 04/28/2023
  • Venue Allegations: Venue is alleged based on Defendant eVenus being incorporated and having a regular and established place of business in New Jersey. For other defendants, venue is alleged based on their partnership with eVenus and planned activities within the district.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) for a generic version of the anesthetic EXPAREL® constitutes an act of infringement of a patent covering specific compositions of bupivacaine multivesicular liposomes.
  • Technical Context: The lawsuit concerns extended-release local anesthetics that use microscopic, multi-chambered lipid spheres (multivesicular liposomes) to deliver a drug over several days, offering a non-opioid alternative for post-surgical pain management.
  • Key Procedural History: This case is the third action between the parties concerning Defendants' proposed generic EXPAREL® product. Two prior actions, asserting related patents ('495 and '336) against the same ANDA, were filed in 2021 and 2022 and have been consolidated. A claim construction (Markman) hearing was held in the consolidated cases in March 2023, but no order has been issued.

Case Timeline

Date Event
2011-10-28 FDA approves commercial marketing of EXPAREL®
2021-01-22 Earliest Priority Date for U.S. Patent No. 11,426,348
2021-11-08 Pacira files first Hatch-Waxman suit against eVenus and Jiangsu Hengrui
2022-02-10 Pacira files second patent lawsuit against eVenus and Jiangsu Hengrui
2022-08-30 U.S. Patent No. 11,426,348 issues
2022-09-02 The '348 patent is listed in the FDA's Orange Book
2023-04-28 Complaint filed in the instant action

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

U.S. Patent No. 11,426,348 - "Compositions of Bupivacaine Multivesicular Liposomes"

  • Patent Identification: U.S. Patent No. 11,426,348, "Compositions of Bupivacaine Multivesicular Liposomes," issued August 30, 2022. (Compl. ¶58).

The Invention Explained

  • Problem Addressed: The patent addresses the "urgent need for new and improved large scale productions of Exparel®" to meet market demand ('348 Patent, col. 1:40-45). The complaint elaborates that scaling up the manufacturing process is complex, as it is highly sensitive to process conditions like pH and timing, which can lead to drug crystallization and batch failure (Compl. ¶¶12-14).
  • The Patented Solution: The invention is directed to compositions of bupivacaine encapsulated in multivesicular liposomes (MVLs) that result from an improved, scaled-up manufacturing process ('348 Patent, Abstract). The complaint includes a diagram showing a cross-section of an MVL, illustrating its structure of multiple internal chambers composed of lipid membranes that contain and slowly release bupivacaine (Compl. ¶11). This scaled-up process, involving multiple emulsion steps, unexpectedly yields compositions with enhanced stability, characterized by lower levels of lipid degradation byproducts (e.g., erucic acid) and higher internal concentrations of stabilizing agents like lysine compared to batches from prior, smaller-scale processes (Compl. ¶¶15, 62, 64-65).
  • Technical Importance: The improved commercial-scale process allows for up to a five-fold increase in the final product volume compared to previous methods, enabling the production of larger, more stable batches to meet the significant demand for a non-opioid post-surgical analgesic (Compl. ¶62; '348 Patent, col. 1:40-45).

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1, 2, 19, 21, and 41 ('348 Patent, Claims; Compl. ¶¶62, 66, 85).
  • Independent Claim 1 (Composition Claim):
    • Batches comprising compositions of bupivacaine multivesicular liposomes (MVLs).
    • The MVLs contain bupivacaine inside internal aqueous chambers separated by lipid membranes comprising specific lipids (DEPC, DPPG) and at least one neutral lipid.
    • The MVLs are suspended in an aqueous medium.
    • The batches consistently comprise an erucic acid concentration of less than about 109 µg/mL after storage at 25°C for six months.
  • Independent Claim 19 (Method Claim):
    • A method of treating or ameliorating pain in a subject in need thereof.
    • The method comprises administering a composition of claim 1 to the subject.
  • The complaint asserts representative dependent claims 2 and 41, which further limit the erucic acid concentration and add a limitation for encapsulated lysine concentration, respectively (Compl. ¶62).

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic versions of EXPAREL® (bupivacaine liposome injectable suspension, 133 mg/10 mL and 266 mg/20 mL), as described in ANDA No. 214348 ("Proposed ANDA Products") (Compl. ¶¶16, 68).

Functionality and Market Context

  • The functionality of the Proposed ANDA Products is to serve as a single-dose local anesthetic for post-surgical pain management (Compl. ¶57). The active ingredient, bupivacaine, is encapsulated in multivesicular liposomes, which allows for a gradual, extended release of the drug over several days following injection at a surgical site (Compl. ¶57). A diagram in the complaint illustrates this structure, describing "Particle chambers composed of lipid membranes" from which "Bupivacaine [is] released from particles" (Compl. ¶11).
  • The complaint alleges that for the Proposed ANDA Products to obtain FDA approval, they must be proven to be bioequivalent to EXPAREL® (Compl. ¶63). EXPAREL® is described as a "first-of-its-kind" anesthetic and a "significant advance in the field of anesthesiology" because it reduces the need for opioids (Compl. ¶57).

IV. Analysis of Infringement Allegations

’348 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Batches comprising compositions of bupivacaine multivesicular liposomes (MVLs), comprising: (a) bupivacaine residing inside a plurality of internal aqueous chambers of the MVLS separated by lipid membranes, wherein the lipid membranes comprise 1,2,-dierucoylphosphadtidylcholine (DEPC), 1, 2-dipalmitoyl-sn-glycero-3 phospho-rac-(1-glycerol) (DPPG), and at least one neutral lipid; The complaint alleges Defendants' Proposed ANDA Products will meet these limitations because they must be bioequivalent to EXPAREL® to gain FDA approval. It is noted that Defendants did not dispute similar limitations for related patents in prior correspondence. ¶63 col. 13:31-44
(b) and an aqueous medium in which the bupivacaine encapsulated MVLs are suspended; The complaint alleges this limitation will be met based on the requirement that the Proposed ANDA Products be bioequivalent to EXPAREL®. ¶63 col. 13:41-44
(c) wherein the batches consistently comprise an erucic acid concentration of less than about 109 µg/mL after the compositions are stored at 25°C for six months. The complaint alleges that the Proposed ANDA Products will meet this limitation, which describes an unexpected property of large-batch manufacturing. It notes that Defendants did not dispute a similar limitation (about 99 µg/mL) for related patents in prior correspondence. ¶64 col. 14:60-col. 15:2

Identified Points of Contention

  • Scope Questions: The complaint alleges infringement based in part on the regulatory requirement for bioequivalence (Compl. ¶63). A central question is whether demonstrating bioequivalence to EXPAREL® is sufficient to prove that the generic product will meet the specific, novel chemical stability and composition limitations of the '348 patent, which was issued long after EXPAREL®'s initial approval.
  • Technical Questions: Claim 1 requires that batches "consistently" meet the erucic acid limitation. The pre-suit communications indicate a dispute over this term's meaning (Compl. ¶¶6-7). A key technical question will be what level of batch-to-batch uniformity is required by this term, and what evidence Plaintiff can marshall to show the Defendants' yet-to-be-marketed product will meet that standard.

V. Key Claim Terms for Construction

  • The Term: "consistently comprise" (Claim 1)

  • Context and Importance: This term is critical as it quantifies the required uniformity of the claimed chemical property (low erucic acid) across different manufactured batches of the accused product. The complaint notes that the parties have already disagreed on whether this term requires construction, signaling it will be a focal point of the dispute (Compl. ¶¶6-7). Practitioners may focus on this term because its interpretation—whether it implies a strict, near-universal compliance or a more lenient statistical average—could be dispositive for infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent does not provide a special definition, which may support an argument that the term should be given its plain and ordinary meaning, suggesting a high degree of regularity and freedom from variation across all batches.
    • Evidence for a Narrower Interpretation: The patent's examples test three batches and report results as an average with a low Relative Standard Deviation (%RSD) (e.g., '348 Patent, Table 1A). A party could argue "consistently" should be interpreted in light of these examples, tying the standard to a specific statistical measure of variance acceptable in pharmaceutical manufacturing, rather than absolute uniformity.

  • The Term: "about" (Claims 1, 2, 41, etc.)

  • Context and Importance: This term modifies several critical numerical limitations, including the erucic acid concentration ("about 109 µg/mL") and lysine concentration ("about 0.03 mg/mL"). Its scope will define the permissible margin of error or variance for these values, directly impacting the infringement analysis.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: Parties may argue that "about" accounts for normal experimental and manufacturing variability, and its scope should be determined by the understanding of a person of ordinary skill in the art.
    • Evidence for a Narrower Interpretation: The patent provides specific data points in its examples. For instance, dependent claim 2 recites "about 99 µg/mL," and the corresponding data in Table 1A shows an average of 98.7 µg/mL with a very low %RSD of 0.6 ('348 Patent, Table 1A). A party could argue this demonstrates the inventors' intent for "about" to cover a very narrow range around the stated number.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement of method claims 19 and 21, asserting that the labeling for the Proposed ANDA Products will instruct healthcare providers to administer the product for pain treatment, which constitutes the patented method (Compl. ¶¶96-98). Contributory infringement is also alleged, based on the assertion that the product is especially made for this infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶77, 113-114).
  • Willful Infringement: Willfulness is alleged based on Defendants' knowledge of the '348 patent, with the complaint citing Defendants' service of the Paragraph IV Notice Letter as evidence of actual knowledge (Compl. ¶¶75, 92).

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

  • A core issue will be one of proof of infringement in a Hatch-Waxman context: Can Plaintiff prove, by a preponderance of the evidence, that Defendants' proposed generic product will necessarily meet the specific product-by-process-style limitations of the '348 patent (e.g., erucic acid levels after six months of storage), when those allegations are based on regulatory requirements for bioequivalence and inferences about a product not yet on the market?
  • A central question of claim construction will be the scope of the term "consistently" in claim 1. The resolution of whether this term requires near-perfect uniformity across all batches or allows for a degree of statistical variation will be critical to the infringement analysis.
  • The case presents a key evidentiary question: Does the fact that the claimed product characteristics were "unexpected" results of a specific, scaled-up manufacturing process (Compl. ¶¶15, 62) require Plaintiff to prove that Defendants will use a sufficiently similar process, or is it enough to show the final generic product will, for whatever reason, exhibit those same characteristics?