DCT

2:21-cv-19829

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: Pacira Pharmaceuticals, Inc. v. eVenus Pharmaceuticals Laboratories Inc., 2:21-cv-19829, D.N.J., 11/08/2021
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant eVenus being incorporated and having a regular and established place of business in the state. Venue over its Chinese parent, Jiangsu Hengrui, is asserted based on its alleged control over eVenus, its contacts with the United States, and its status as a foreign corporation.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) for a generic bupivacaine liposome injectable suspension constitutes an act of infringement of a patent covering specific manufacturing processes and the resulting stable drug composition.
  • Technical Context: The technology concerns large-scale manufacturing of extended-release local anesthetics using multivesicular liposomes, a field important for advancing post-surgical pain management and reducing opioid dependency.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Defendants' filing of an ANDA with a Paragraph IV certification, which asserts that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. The complaint was filed within the 45-day statutory window, triggering an automatic 30-month stay of FDA approval for the generic drug.

Case Timeline

Date Event
2021-01-22 '495 Patent Priority Date
2021-06-15 '495 Patent Issue Date
2021-09-20 Defendants provide notice of ANDA filing to Plaintiff
2021-11-08 Complaint Filing Date

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

U.S. Patent No. 11,033,495 - Manufacturing of Bupivacaine Multivesicular Liposomes, issued June 15, 2021

The Invention Explained

  • Problem Addressed: The patent background section notes an "urgent need for new and improved large scale productions of Exparel®" to satisfy substantial and growing market demand, suggesting that prior manufacturing methods were insufficient for the required scale ('495 Patent, col. 1:33-36).
  • The Patented Solution: The patent describes a commercial-scale, double-emulsion process for creating bupivacaine encapsulated in multivesicular liposomes (MVLs). The process starts by creating a water-in-oil emulsion and then mixing it into a second aqueous solution to form a water-in-oil-in-water emulsion, followed by solvent removal and a series of filtration steps ('495 Patent, col. 10:45-col. 11:2). This specific manufacturing method is claimed to produce a final composition with defined chemical properties, including a low concentration of erucic acid, a lipid degradation byproduct, which indicates improved stability ('495 Patent, Claim 1).
  • Technical Importance: The described process purports to yield a more stabilized form of bupivacaine-encapsulated MVLs with fewer byproducts, a critical attribute for ensuring pharmaceutical quality, safety, and shelf-life, particularly at a commercial manufacturing scale ('495 Patent, col. 3:38-40).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the '495 patent (Compl. ¶50). Independent claim 1 is a representative composition-by-process claim.
  • Claim 1 recites a composition of bupivacaine encapsulated multivesicular liposomes (MVLs) prepared by a "commercial scale process" with the following essential elements:
    • (a) mixing a first aqueous solution (phosphoric acid) with a volatile water-immiscible solvent solution (containing bupivacaine, DEPC, DPPG, and a neutral lipid) to form a water-in-oil emulsion;
    • (b) mixing that emulsion with a second aqueous solution (containing lysine and dextrose) to form a water-in-oil-in-water emulsion;
    • (c) removing the solvent to create an aqueous suspension of the MVLs;
    • (d)-(f) performing a sequence of microfiltration and diafiltration steps to concentrate the MVLs and exchange the suspension liquid, resulting in a final bupivacaine concentration of about 12.6 mg/mL to 17.0 mg/mL;
    • performing all steps under aseptic conditions; and
    • the resulting composition having an erucic acid concentration of "about 23 µg/mL or less" after storage at 25° C for one month.
  • The complaint's general allegation suggests a reservation of the right to assert other claims, including dependent claims that further narrow these process steps and composition characteristics.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the "eVenus ANDA Product," a proposed generic version of EXPAREL® (bupivacaine liposome injectable suspension, 13.3 mg/mL), for which Defendants have filed ANDA No. 214348 with the FDA (Compl. ¶¶ 1, 4, 7).

Functionality and Market Context

The infringement claim is a statutory act under the Hatch-Waxman framework, based on the submission of the ANDA itself rather than on a currently marketed product (Compl. ¶51). The complaint alleges that the purpose of the ANDA is to obtain approval for the commercial manufacture and sale of a generic equivalent to EXPAREL®, a single-dose local anesthetic used for post-surgical pain management, before the expiration of the ’495 patent (Compl. ¶¶ 36, 40). The complaint states that the eVenus ANDA Product contains bupivacaine as its active ingredient (Compl. ¶44).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

  • '495 Patent Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A composition of bupivacaine encapsulated multivesicular liposomes (MVLs) prepared by a commercial scale process, the commercial scale process comprising: The complaint alleges that the eVenus ANDA Product is a composition covered by the claim and will be manufactured using a process that meets the claim's limitations. ¶50, ¶54 col. 21:45-48
(a) mixing a first aqueous solution comprising phosphoric acid with a volatile water-immiscible solvent solution... to form a water-in-oil first emulsion... The complaint alleges on information and belief that the manufacture of the eVenus ANDA Product will include this step. ¶54 col. 21:49-59
(b) mixing the water-in-oil first emulsion with a second aqueous solution... to form a water-in-oil-in-water second emulsion... The complaint alleges on information and belief that the manufacture of the eVenus ANDA Product will include this step. ¶54 col. 21:60-65
(c) removing the volatile water-immiscible solvent... to form a first aqueous suspension... The complaint alleges on information and belief that the manufacture of the eVenus ANDA Product will include this step. ¶54 col. 22:1-4
(d) reducing the first volume... by microfiltration... The complaint alleges on information and belief that the manufacture of the eVenus ANDA Product will include this step. ¶54 col. 22:5-9
(e) exchanging the aqueous supernatant... by diafiltration... The complaint alleges on information and belief that the manufacture of the eVenus ANDA Product will include this step. ¶54 col. 22:10-13
(f) further reducing the third volume... by microfiltration to provide a final aqueous suspension... The complaint alleges on information and belief that the manufacture of the eVenus ANDA Product will include this step. ¶54 col. 23:3-8
wherein the erucic acid concentration in the composition is about 23 µg/mL or less after the composition is stored at 25° C. for one month. The complaint alleges that the resulting eVenus ANDA Product is covered by the claim, which suggests it will meet this product characteristic. ¶50 col. 23:12-15
  • Identified Points of Contention:
    • Scope Questions: As Claim 1 is a composition-by-process claim, a primary question for the court will be whether the claim's scope is limited to compositions made by the exact process recited. The infringement analysis will turn on whether the manufacturing process detailed in Defendants' confidential ANDA can be shown to meet every limitation of the claimed process.
    • Technical Questions: A central factual question is whether the final eVenus ANDA Product, once produced, actually meets the quantitative limitation for "erucic acid concentration." The interpretation of "about 23 µg/mL" will be a key point of dispute, requiring expert testimony and testing of the ANDA product samples.

V. Key Claim Terms for Construction

  • The Term: "commercial scale process"

  • Context and Importance: This term appears in the preamble of Claim 1 and defines the context for the entire claim. Its construction is critical because infringement will depend on whether the process described in Defendants' ANDA qualifies as "commercial scale."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent contrasts the invention with prior art in the context of meeting "substantial and growing market demand" ('495 Patent, col. 1:35-36), which may support an interpretation that any process intended for commercial distribution, regardless of specific batch size, qualifies.
    • Evidence for a Narrower Interpretation: Practitioners for the defense may argue the term is limited by specific disclosures in the specification, such as the description of producing final volumes of "about 150 L to about 250 L" ('495 Patent, col. 15:45-48), potentially setting a high quantitative threshold for what constitutes "commercial scale."

  • The Term: "about 23 µg/mL or less"

  • Context and Importance: This term sets a specific, measurable limit on a key impurity and product stability marker. The scope of "about" will be determinative for the infringement analysis of this limitation.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party may argue that "about" should be interpreted to encompass the range of normal experimental and measurement variability inherent in the analytical techniques used, such as HPLC ('495 Patent, col. 19:45-48). The patent's own data shows slight variations around averages (e.g., an average of 22.7 µg/mL from batches of 22 and 23 µg/mL), which could support a more flexible reading ('495 Patent, Table 1A).
    • Evidence for a Narrower Interpretation: A party may argue for a more restrictive meaning, contending that "about" does not grant a wide berth and is cabined by the precision implied by the patent's own examples. For instance, they might argue that a value of 24 µg/mL is definitively not "about 23 µg/mL."

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Defendants will induce infringement by marketing and distributing the eVenus ANDA Product with a product label that instructs healthcare professionals and other end-users to administer it in a manner that infringes the '495 patent (Compl. ¶¶ 55-56). It further alleges contributory infringement, stating the product is not a staple article of commerce and is especially adapted for an infringing use (Compl. ¶58).
  • Willful Infringement: The complaint alleges willful infringement based on Defendants having acted with full knowledge of the '495 patent, as evidenced by their filing of a Paragraph IV certification, and allegedly without a reasonable basis for their belief of non-infringement or invalidity (Compl. ¶62).

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

  • A core issue will be one of process-product scope: Given the composition-by-process format of Claim 1, to what extent must the Defendants' manufacturing method, as detailed in their confidential ANDA, mirror the specific steps recited in the claim for the resulting product to be found infringing?
  • A second key issue will be a quantitative evidentiary question: Does the accused generic product, when manufactured according to its ANDA, actually possess an "erucic acid concentration" that falls within the scope of "about 23 µg/mL or less" after one month at 25° C? The resolution will depend heavily on the court's construction of the term "about" and the results of competing expert analyses.