DCT

2:24-cv-07680

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-07680, D.N.J., 07/10/2024
  • Venue Allegations: Venue is alleged based on Defendant eVenus being incorporated and having its principal place of business in New Jersey, and on all defendants allegedly conducting business, committing acts of infringement, and having established places of business within the district.
  • Core Dispute: Plaintiff alleges that Defendants’ generic bupivacaine liposome injectable suspension, for which they received FDA approval via an Abbreviated New Drug Application (ANDA), infringes a patent covering specific compositions of the brand-name drug, EXPAREL®.
  • Technical Context: The technology involves multivesicular liposomes (MVLs), which are microscopic spherical particles that encapsulate the local anesthetic bupivacaine to provide extended, non-opioid pain relief after surgery.
  • Key Procedural History: This lawsuit is the latest in a series of at least four prior patent infringement actions between the same parties concerning the same accused generic product and related patents from the same family. The complaint notes that a five-day bench trial concerning a related patent concluded in February 2024. Significantly, the complaint alleges that during the prosecution of the patent-in-suit, the Plaintiff disclosed to the USPTO the Defendants' invalidity and inequitable conduct arguments and expert reports from the prior litigation, after which the patent was granted.

Case Timeline

Date Event
2011-10-28 FDA approves Pacira's New Drug Application for EXPAREL®
2021-01-22 Earliest Priority Date for U.S. Patent No. 11,925,706
2021-11-08 Pacira files first patent lawsuit against Defendants
2022-02-10 Pacira files second patent lawsuit against Defendants
2022-08-30 U.S. Patent No. 11,426,348 issues
2023-04-28 Pacira files third patent lawsuit against Defendants
2023-11-21 U.S. Patent Nos. 11,819,574 and 11,819,575 issue
2024-02-06 Five-day bench trial begins in prior litigation
2024-03-12 U.S. Patent No. 11,925,706 issues
2024-05-20 Pacira files fourth patent lawsuit against Defendants
2024-07-01 FDA approves Defendants' ANDA for generic bupivacaine
2024-07-10 Complaint filed in present action

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

U.S. Patent No. 11,925,706 - "Manufacturing of Bupivacaine Multivesicular Liposomes"

  • Issued: March 12, 2024

The Invention Explained

  • Problem Addressed: The patent addresses the challenges of producing bupivacaine-encapsulated multivesicular liposomes (MVLs) at a commercial scale (Compl. ¶¶ 10, 12). Such products are inherently unstable during manufacturing, and scaling up the process from a laboratory batch to a commercial batch (e.g., 200L) presents significant technical hurdles, particularly in controlling the two critical emulsification steps to form the complex honeycomb structure of the MVLs (’706 Patent, col. 1:28-35; Compl. ¶¶ 10-12).
  • The Patented Solution: The patent claims compositions of MVLs that result from an improved, scaled-up manufacturing process. These compositions are defined by specific, unexpected characteristics: a higher internal concentration of lysine and improved stability, as measured by a lower concentration of a specific lipid degradation product (erucic acid) over time, compared to earlier formulations (Compl. ¶¶ 13, 62; ’706 Patent, Abstract). The complaint includes a cross-sectional diagram of an MVL, illustrating the internal particle chambers composed of lipid membranes from which bupivacaine is slowly released (Compl. p. 6).
  • Technical Importance: This technology provides a more stable formulation of a long-acting local anesthetic, which is critical for meeting the growing market demand for effective non-opioid postsurgical pain management (Compl. ¶57; ’706 Patent, col. 1:45-53).

Key Claims at a Glance

  • The complaint asserts independent composition claim 1 and dependent method claims 12 and 13 (Compl. ¶¶ 62, 64).
  • The essential elements of independent claim 1 are:
    • A composition of bupivacaine encapsulated multivesicular liposomes (MVLs).
    • The MVLs comprise bupivacaine in internal aqueous chambers separated by lipid membranes (containing DEPC, DPPG, cholesterol, a neutral lipid), with the internal chambers also containing lysine.
    • The MVLs are suspended in an aqueous medium that also contains unencapsulated bupivacaine.
    • The total bupivacaine concentration is between about 11.3 mg/mL and 17.0 mg/mL.
    • The erucic acid concentration is below specified thresholds (≤53 µg/mL at 3 months; ≤99 µg/mL at 6 months) when stored at 25°C.
    • The encapsulated lysine concentration is at least about 0.03 mg/mL.

III. The Accused Instrumentality

Product Identification

The accused products are the generic versions of EXPAREL® for which Defendants obtained approval under ANDA No. 214348 (Compl. ¶¶ 8, 16). The products are bupivacaine liposome injectable suspensions in two dosage forms: 133 mg/10 mL and 266 mg/20 mL (13.3 mg/mL) (Compl. ¶16).

Functionality and Market Context

The accused products are designed to be therapeutic equivalents to Pacira's EXPAREL®, a first-of-its-kind, single-dose local anesthetic (Compl. ¶¶ 1, 57). The functionality relies on encapsulating bupivacaine in MVLs to achieve gradual release over several days, providing prolonged postsurgical pain control and reducing the need for opioids (Compl. ¶57). The complaint includes a screenshot from the FDA database confirming the approval of Defendants' ANDA on July 1, 2024 (Compl. ¶8). The products are positioned to compete directly with EXPAREL® as lower-cost generic alternatives (Compl. ¶16).

IV. Analysis of Infringement Allegations

'706 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A composition of bupivacaine encapsulated multivesicular liposomes (MVLs), comprising: a) bupivacaine encapsulated MVLs comprising bupivacaine residing inside a plurality of internal aqueous chambers...separated by lipid membranes, wherein the lipid membranes comprise...DEPC...DPPG, cholesterol, and at least one neutral lipid, the plurality of internal aqueous chambers of the MVLs also comprise lysine; and b) an aqueous medium in which the bupivacaine encapsulated MVLs are suspended... On information and belief, Defendants' ANDA products are bupivacaine MVL products containing the claimed components. ¶63 col. 18:1-6
c) wherein the bupivacaine concentration in the composition is from about 11.3 mg/mL to about 17.0 mg/mL; On information and belief, the ANDA products have this concentration, a fact Defendants allegedly did not dispute in a notice letter regarding related patents. ¶63 col. 18:7-9
d) wherein an erucic acid concentration in the composition is about 53 µg/mL or less when...stored at 25° C. for three months, and the erucic acid concentration...is about 99 µg/mL or less when...stored at 25° C. for six months; On information and belief, the ANDA products will meet these stability marker limitations. The complaint notes that Defendants did not dispute the six-month limitation in a prior notice letter concerning related patents. ¶63, ¶19 col. 18:10-14
e) wherein the encapsulated lysine concentration in the composition is at least about 0.03 mg/mL. On information and belief, the ANDA products will meet this limitation, which the complaint describes as an unexpected result of Pacira's scaled-up process that confers stability benefits. ¶63, ¶20 col. 18:15-17

Identified Points of Contention

  • Technical Questions: A primary technical question is whether Defendants' generic product, which is likely manufactured using a different process, will actually exhibit the specific quantitative properties recited in limitations (d) and (e) of claim 1. The complaint alleges infringement based on "information and belief" and Defendants' alleged non-dispute of similar limitations in prior litigation correspondence (Compl. ¶63). The case will depend on whether discovery and product testing confirm that the accused product has the claimed erucic acid degradation profile and internal lysine concentration.
  • Scope Questions: The claims recite specific quantitative ranges (e.g., "about 53 µg/mL or less," "at least about 0.03 mg/mL"). The interpretation of the term "about" could become a central issue in determining the literal scope of the claims and whether the measured values from Defendants' product fall within that scope.

V. Key Claim Terms for Construction

  • The Term: "wherein an erucic acid concentration in the composition is about 53 µg/mL or less when measured after the composition is stored at 25° C. for three months" (and the related six-month limitation).

    • Context and Importance: This limitation defines the invention by its stability profile, a characteristic that allegedly results from Pacira's proprietary scaled-up manufacturing process. Practitioners may focus on this term because it is a "product-by-process" style limitation that will require factual evidence from testing the accused product. The infringement analysis for this key differentiating feature will be entirely evidentiary.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A plaintiff may argue that the claim language is clear and covers any composition that meets the specified erucic acid threshold, regardless of the process used to make it. The specification presents this stability as an objective, measurable property of the improved final product (’706 Patent, Table 1A, col. 21).
      • Evidence for a Narrower Interpretation: A defendant may argue that this limitation is inextricably linked to the specific manufacturing process detailed in the specification. They could point to specification language emphasizing that these improved stability properties are a direct, unexpected result of the "newly developed processes" (’706 Patent, col. 3:45-56), suggesting that products made by a different process are not contemplated by the claim.

  • The Term: "wherein the encapsulated lysine concentration in the composition is at least about 0.03 mg/mL."

    • Context and Importance: This limitation is critical because the complaint frames it as a counter-intuitive and unexpected discovery that provides enhanced stability (Compl. ¶¶ 13, 20). Proving that the accused product meets this minimum internal lysine level will be a key factual battleground for infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The plain language of the claim sets a clear quantitative floor. Pacira will argue that any product meeting this measurable threshold infringes. The patent claims the resulting composition, not the intent behind the manufacturing process (’706 Patent, claim 1).
      • Evidence for a Narrower Interpretation: A defendant could argue their process is designed to minimize internal lysine, consistent with the "conventional wisdom" cited in the complaint (Compl. ¶20). They may assert that any measured lysine in their product is a trivial and unintended impurity, not the functional, intentional component described in the patent, and thus falls outside the scope of the claim.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement of method claims 12 and 13. It asserts that Defendants' product labeling will instruct and encourage healthcare providers to administer the product via local infiltration to a surgical site for analgesia, which is the method recited in the claims (Compl. ¶¶ 65, 94). The complaint also alleges contributory infringement, stating the product is especially adapted for this infringing use and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶¶ 75, 109).
  • Willful Infringement: The complaint alleges that Defendants had knowledge of the ’706 patent no later than its issuance and listing in the FDA's Orange Book on March 15, 2024 (Compl. ¶90). It further points to Defendants' service of a Paragraph IV certification notice letter as evidence of actual knowledge of the patent, forming a basis for willfulness (Compl. ¶¶ 73, 89).

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

  • A central issue will be one of evidentiary proof: Can Pacira demonstrate through discovery and empirical testing that the Defendants' generic product, despite likely being made through a different process, possesses the specific and narrow compositional characteristics (i.e., the erucic acid degradation profile and minimum encapsulated lysine concentration) required by claim 1?
  • A key legal and factual question will be one of validity in context: Given that the patent examiner reviewed invalidity arguments and expert reports from prior litigation before allowing the '706 patent, the case will test whether these specific quantitative limitations are sufficient to render the claims non-obvious over the prior art, and whether Defendants can present new evidence or arguments to overcome the patent's presumption of validity.