DCT

2:25-cv-06742

Pacira Pharma Inc v. Qilu Pharmaceutical Hainan Co Ltd

Log In
Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:25-cv-06742, E.D. Pa., 12/01/2025
  • Venue Allegations: Venue is asserted based on Defendant Qilu Pharma, Inc.'s residence in Pennsylvania and allegations that both Defendants committed acts of infringement in the district, including the submission of an Abbreviated New Drug Application (ANDA) to the FDA.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an ANDA to market a generic version of the post-operative pain-management drug EXPAREL® infringes nine U.S. patents related to the drug's formulation, manufacturing processes, and methods of treatment.
  • Technical Context: The technology relates to extended-release drug delivery using multivesicular liposomes (MVLs) to encapsulate the anesthetic bupivacaine, providing a non-opioid option for managing post-surgical pain.
  • Key Procedural History: U.S. Patent No. 11,033,495 was previously litigated, resulting in a district court finding of invalidity for one claim, which was subsequently settled on appeal. The same patent also underwent an ex parte reexamination at the USPTO, which confirmed the patentability of its claims, including 88 newly added claims, over the art and arguments from the prior litigation.

Case Timeline

Date Event
2011-10-28 FDA approves commercial marketing of EXPAREL
2021-01-22 Earliest Priority Date for ’495, ’574, ’890, ’024, and ’047 Patents
2021-06-15 U.S. Patent No. 11,033,495 Issues
2023-11-21 U.S. Patent No. 11,819,574 Issues
2024-02-01 Trial held in prior litigation involving the ’495 Patent
2024-05-20 Earliest Priority Date for ’483, ’940, ’468, and ’142 Patents
2024-11-19 U.S. Patent No. 12,144,890 Issues
2024-11-26 U.S. Patent No. 12,151,024 Issues
2024-12-03 U.S. Patent No. 12,156,940 Issues
2025-03-18 U.S. Patent No. 12,251,468 Issues
2025-05-13 U.S. Patent No. 12,296,047 Issues
2025-06-03 U.S. Patent No. 12,318,483 Issues
2025-07-29 U.S. Patent No. 12,370,142 Issues
2025-08-19 USPTO issues ex parte reexamination certificate for the ’495 Patent
2025-10-20 Defendants send Qilu Notice Letter regarding ANDA submission
2025-11-13 Plaintiff's counsel sends letter to Defendants regarding ANDA access
2025-12-01 Complaint filed

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 addresses the need for new and improved large-scale manufacturing processes for EXPAREL® (bupivacaine multivesicular liposomes) to meet growing market demand, which prior smaller-scale processes could not satisfy while maintaining product quality (Compl. ¶¶ 38, 41; ’495 Patent, col. 1:32-36).
  • The Patented Solution: The invention describes a commercial-scale process for preparing bupivacaine encapsulated in multivesicular liposomes (MVLs). The process involves specific steps of creating a water-in-oil emulsion, a subsequent water-in-oil-in-water emulsion, removing the solvent, and then using microfiltration and diafiltration to purify and concentrate the product ('495 Patent, col. 2:55-col. 3:20). This process yields a composition with improved stability, as indicated by a lower concentration of erucic acid (a lipid degradation product) after storage ('495 Patent, col. 16:21-26, Fig. 3B).
  • Technical Importance: The described process improvements enabled a scaled-up manufacturing capacity for EXPAREL, a non-opioid analgesic, which is significant given the context of the opioid epidemic (Compl. ¶¶ 1, 40; ’495 Patent, col. 1:32-36).

Key Claims at a Glance

  • The complaint alleges infringement of one or more unspecified claims of the '495 patent (Compl. ¶105). Independent claim 1 is a representative composition-by-process claim.
  • Essential Elements of Independent Claim 1:
    • A composition of bupivacaine encapsulated multivesicular liposomes (MVLs) prepared by a commercial scale process.
    • The process comprises steps of: (a) mixing an aqueous phosphoric acid solution with a volatile water-immiscible solvent solution containing bupivacaine and specific lipids to form a first emulsion; (b) mixing the first emulsion with a second aqueous solution to form a second emulsion; (c) removing the volatile solvent to form a first aqueous suspension of MVLs; (d) reducing the volume by microfiltration; (e) exchanging the supernatant with a saline solution by diafiltration; and (f) further reducing the volume by microfiltration to a target concentration.
    • The resulting composition has an erucic acid concentration of about 23 µg/mL or less after being stored at 25° C. for one month.
  • The complaint does not explicitly reserve the right to assert dependent claims, but this is standard practice.

U.S. Patent No. 11,819,574 - "Manufacturing of bupivacaine multivesicular liposomes"

Issued November 21, 2023

The Invention Explained

  • Problem Addressed: Similar to the '495 patent, this patent addresses the challenges of scaling up the manufacturing of MVL drug products, which are inherently unstable, and the difficulty of maintaining quality and stability at larger production volumes (Compl. ¶¶ 38, 41; ’574 Patent, col. 1:20-37).
  • The Patented Solution: The invention claims batches of bupivacaine MVL compositions produced by a commercial-scale process. The claims define the batches by specific, measurable characteristics related to their stability over time, such as having a low average rate of change in the cumulative percentage release of bupivacaine when tested using a specified in vitro release assay after 12 months of storage ('574 Patent, Abstract; col. 3:45-col. 4:49). This indicates a more stable and predictable drug release profile over the product's shelf life.
  • Technical Importance: By defining product batches with specific, improved stability and release profiles, the invention provides a basis for ensuring consistent quality and performance for a scaled-up, commercially produced non-opioid analgesic (Compl. ¶¶ 37-38).

Key Claims at a Glance

  • The complaint alleges infringement of one or more unspecified claims of the '574 patent (Compl. ¶139). Independent claim 1 is a representative claim directed to batches of the composition.
  • Essential Elements of Independent Claim 1:
    • Batches comprising compositions of bupivacaine encapsulated MVLs, where each batch has a volume of 100 L to 250 L.
    • The batches have an average erucic acid concentration of about 105 µg/mL or less when measured after storage at 25° C. for six months.
    • Each batch has a cumulative percentage release of bupivacaine from 46% to 71% at a 24-hour time point, measured from six aliquots after 12 months of storage.
    • The batches exhibit an average rate of change in the cumulative percentage release at the 24-hour time point of at least 0.05%/month after 12 months of storage.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 12,144,890 - "Manufacturing of bupivacaine multivesicular liposomes"

Issued November 19, 2024

  • Patent Identification: U.S. Patent No. 12,144,890, "Manufacturing of bupivacaine multivesicular liposomes," issued November 19, 2024 (Compl. ¶54).
  • Technology Synopsis: This patent, part of the "Erucic Acid Patents" family, is directed to Pacira's scaled-up manufacturing process for EXPAREL (Compl. ¶37). The claims cover processes of preparing bupivacaine encapsulated in MVLs, focusing on achieving specific stability and release characteristics, such as a defined low rate of change in drug release over time (Compl. ¶55; '890 Patent, col. 23:2-24).
  • Asserted Claims: The complaint asserts one or more unspecified claims (Compl. ¶173). Independent claim 1 is representative.
  • Accused Features: Defendants' ANDA product and its use are alleged to be covered by the claims (Compl. ¶173).

U.S. Patent No. 12,151,024 - "Manufacturing of bupivacaine multivesicular liposomes"

Issued November 26, 2024

  • Patent Identification: U.S. Patent No. 12,151,024, "Manufacturing of bupivacaine multivesicular liposomes," issued November 26, 2024 (Compl. ¶58).
  • Technology Synopsis: Also in the "Erucic Acid Patents" family, this patent claims compositions of bupivacaine-encapsulated MVLs (Compl. ¶¶ 37, 59). The claims define the product by its specific particle size distribution (d90 particle diameter) and stability metrics (erucic acid concentration after storage), reflecting improvements from the scaled-up manufacturing process (Compl. ¶¶ 43, 59; '024 Patent, Abstract).
  • Asserted Claims: The complaint asserts one or more unspecified claims (Compl. ¶207). Independent claim 1 is representative.
  • Accused Features: Defendants' ANDA product is alleged to be a composition covered by the claims (Compl. ¶207).

U.S. Patent No. 12,296,047 - "Manufacturing of bupivacaine multivesicular liposomes"

Issued May 13, 2025

  • Patent Identification: U.S. Patent No. 12,296,047, "Manufacturing of bupivacaine multivesicular liposomes," issued May 13, 2025 (Compl. ¶62).
  • Technology Synopsis: This patent is another member of the "Erucic Acid Patents" family and claims processes for preparing a batch of bupivacaine encapsulated MVLs (Compl. ¶¶ 37, 63). The claims focus on achieving a specific particle size distribution and a low erucic acid concentration after storage, which are outcomes of the improved, scaled-up process ('047 Patent, col. 27:8-47).
  • Asserted Claims: The complaint asserts one or more unspecified claims (Compl. ¶241). Independent claim 16 is representative.
  • Accused Features: The process used to make Defendants' ANDA product is alleged to infringe (Compl. ¶241).

U.S. Patent No. 12,318,483 - "Manufacturing of bupivacaine multivesicular liposomes"

Issued June 3, 2025

  • Patent Identification: U.S. Patent No. 12,318,483, "Manufacturing of bupivacaine multivesicular liposomes," issued June 3, 2025 (Compl. ¶68).
  • Technology Synopsis: This "Method of Treatment Patent" claims methods of treating pain by administering a composition of bupivacaine-encapsulated MVLs (Compl. ¶¶ 68-69). The claims specify administration via an adductor canal block or a sciatic nerve block to provide regional analgesia, consistent with EXPAREL's FDA-approved labeling (Compl. ¶67; '483 Patent, Abstract).
  • Asserted Claims: The complaint asserts one or more unspecified claims (Compl. ¶275). Independent claim 1 is representative.
  • Accused Features: The use of Defendants' ANDA product, as will be directed by its proposed labeling, is alleged to infringe (Compl. ¶¶ 275, 280).

U.S. Patent Nos. 12,156,940, 12,251,468, and 12,370,142 (The "IVRA Patents")

  • Patent Identification: These three patents are identified as the "In Vitro Release Assay ('IVRA') Patents" (Compl. ¶74).
    • U.S. Patent No. 12,156,940, issued December 3, 2024 (Compl. ¶78).
    • U.S. Patent No. 12,251,468, issued March 18, 2025 (Compl. ¶82).
    • U.S. Patent No. 12,370,142, issued July 29, 2025 (Compl. ¶86).
  • Technology Synopsis: This patent family describes a new manufacturing process that allegedly provides larger batch sizes and an improved in vitro release stability profile compared to prior processes (Compl. ¶74). The complaint includes Figure 3A, a line chart illustrating that batches from the new process show a flat or slightly upward trend in the rate of change of bupivacaine release over 12 months, in contrast to older processes which trend downward (Compl. ¶¶ 76-77). This improved stability profile is a key feature of the claimed inventions (see, e.g., '940 Patent, Abstract).
  • Asserted Claims: The complaint asserts one or more unspecified claims for each patent (Compl. ¶¶ 309, 343, 377).
  • Accused Features: The batches of Defendants' ANDA product are alleged to be compositions covered by the claims of the '940 and '468 patents, and the process for preparing them is alleged to be covered by the claims of the '142 patent (Compl. ¶¶ 79, 83, 87).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Qilu's ANDA Product," a purported generic version of EXPAREL® (bupivacaine liposome injectable suspension) for which Defendants have filed ANDA No. 220830 with the FDA (Compl. ¶12).

Functionality and Market Context

  • The complaint alleges that Qilu's ANDA Product is an injectable suspension containing bupivacaine as its active ingredient, encapsulated within microscopic, spherical multivesicular liposome ("MVL") particles (Compl. ¶¶ 39, 96). A cross-sectional diagram in the complaint illustrates how bupivacaine is contained within and released from the particle chambers of an MVL (Compl. ¶39). The product is designed for extended release to manage post-surgical pain (Compl. ¶1).
  • Defendants are seeking FDA approval for the same dosages as EXPAREL: 266 mg/20 mL and 133 mg/10mL (Compl. ¶35). The complaint alleges that upon approval, Defendants intend to commercially manufacture, market, and sell this product in the United States as a generic alternative to EXPAREL before the expiration of the patents-in-suit (Compl. ¶¶ 12, 15).

IV. Analysis of Infringement Allegations

The complaint does not contain or reference a claim chart exhibit providing a detailed mapping of the accused product to the asserted patent claims. The infringement theory is presented in narrative form, based on information and belief derived from Defendants' submission of ANDA No. 220830 to the FDA, which identifies EXPAREL as the Reference Listed Drug (Compl. ¶¶ 93, 99).

The central infringement theory is that by filing an ANDA seeking to market a generic version of EXPAREL, Defendants have committed an act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶106). The complaint further alleges that the commercial manufacture, use, and sale of Qilu's ANDA Product after FDA approval would directly infringe the asserted claims covering compositions, manufacturing processes, and methods of use (Compl. ¶107). The infringement allegations are premised on the regulatory requirement that a generic drug must have the same active ingredient, dosage form, strength, and route of administration as the branded drug, suggesting that Qilu's ANDA product will necessarily possess the characteristics claimed in Pacira's patents (Compl. ¶93).

  • Identified Points of Contention:
    • Scope Questions (Product-by-Process Claims): For patents claiming a composition prepared by a specific process (e.g., '495 Patent), a primary question will be whether Defendants' manufacturing process, as detailed in its ANDA, includes all the steps recited in the claims. The procedural history of the '495 patent's reexamination, which added 88 new claims, may introduce complex issues of claim scope and estoppel (Compl. ¶46).
    • Technical Questions (Product and Batch Claims): For patents claiming compositions or batches with specific physical and chemical properties (e.g., '574 and the IVRA patents), the dispute may center on whether Defendants' product will, in fact, exhibit the claimed characteristics. This raises an evidentiary question regarding the stability and in vitro release profiles of Defendants' product, and whether the testing methodologies used to assess those properties align with the claim requirements (Compl. ¶¶ 73-77).
    • Method of Use Claims: For the method of treatment patent ('483 Patent), a key question will be whether the proposed label for Qilu's ANDA Product will instruct or encourage physicians to administer the drug in the specific manner claimed, such as via an adductor canal block (Compl. ¶¶ 67, 69).

V. Key Claim Terms for Construction

"commercial scale process" (from Claim 1 of the ’495 Patent)

Context and Importance

This term appears in the preamble of a product-by-process claim. Its construction will be critical for determining whether the process used to make the accused product falls within the scope of the claims. Practitioners may focus on this term because the patents-in-suit are directed to solving problems that arise specifically during large-scale manufacturing, as distinct from laboratory or small-batch production (Compl. ¶¶ 38, 43).

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The detailed description states that the "newly developed processes provide up to 5 folds increase in final product volume as compared to the current process" ('495 Patent, col. 4:32-34). This could support an interpretation that "commercial scale" is a relative term defined by a significant increase over prior art processes, rather than a specific batch volume.
  • Evidence for a Narrower Interpretation: The specification repeatedly contrasts the new process with prior 45-liter batches and discusses embodiments in the range of 150 L to 250 L ('574 Patent, col. 15:44-48). This may support an argument that "commercial scale" requires a specific, large minimum batch volume (e.g., at least 100 L, as claimed in the '574 patent).

"average rate of change in the cumulative percentage release" (from Claim 1 of the ’574 Patent)

Context and Importance

This term defines a key stability characteristic of the claimed batches of EXPAREL. The infringement analysis will depend on whether the accused product exhibits the claimed rate of change when measured according to the patent's testing protocol. The complaint highlights this as a key innovation, showing data where the new process yields a stable or slightly increasing release rate, unlike older processes (Compl. ¶¶ 76-77).

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The claims themselves do not specify the exact mathematical formula or number of data points required to calculate the "average rate of change," beyond stating it is measured after 12 months of storage. This could support using any scientifically reasonable method, such as a linear regression over several time points.
  • Evidence for a Narrower Interpretation: The specification provides examples where the rate of change is presented as the slope of a line derived from data points at 0, 3, 6, 9, and 12 months (Compl. ¶75; '574 Patent, col. 17:15-20). Defendants may argue that this specific methodology is required to properly determine the "average rate of change" as understood by the inventors. The patent also refers to the "rotator-facilitated in vitro release assay," implying a specific testing apparatus and procedure are required.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement allegation is based on the assertion that Defendants' proposed product labeling will be substantially similar to that of EXPAREL and will instruct healthcare professionals and patients to use the generic product in a manner that directly infringes method-of-use claims (Compl. ¶¶ 111, 281). The contributory infringement allegation is based on the assertion that Qilu's ANDA product is not a staple article of commerce and is especially made for use in an infringing manner (Compl. ¶¶ 113, 283).
  • Willful Infringement: The complaint alleges that Defendants' infringement is willful, based on their knowledge of the patents-in-suit as evidenced by their filing of a Paragraph IV Certification with the FDA (Compl. ¶¶ 116-117). This certification asserts that the patents are invalid, unenforceable, or will not be infringed by the proposed generic product.

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

  • A central issue will be one of process equivalence: For the product-by-process claims, can Pacira demonstrate that the manufacturing process described in Qilu's confidential ANDA includes the specific sequence of emulsion, filtration, and diafiltration steps required by the patents, or will Qilu be able to establish a legally significant difference in its manufacturing method?
  • A key evidentiary question will be one of biopharmaceutical comparability: For the product and batch claims, does Qilu's generic product actually exhibit the specific, nuanced stability and in vitro release profiles claimed by Pacira? This will likely involve a technical dispute over testing methodologies and whether a flatter or slightly increasing drug release rate over time, as highlighted in the complaint, is a feature inherent to any bioequivalent formulation or a distinct, patented invention.
  • A significant legal question will involve the impact of prior proceedings: How will the prior litigation and subsequent ex parte reexamination of the '495 patent influence the construction of its claims? The addition of 88 new claims during reexamination creates a complex record that may give rise to arguments concerning claim differentiation, prosecution history estoppel, and the scope of what was surrendered or confirmed as patentable.