DCT

1:24-cv-12416

Pacira Pharma Inc v. Fresenius Kabi USA LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-12416, N.D. Ill., 12/03/2024
  • Venue Allegations: Plaintiff alleges venue is proper in the Northern District of Illinois because Defendant Fresenius Kabi has a regular and established place of business in the district and has participated in acts of infringement there. Venue is alleged as proper for Jiangsu Hengrui as a foreign company that may be sued in any district.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of EXPAREL® infringes a patent directed to batches of bupivacaine multivesicular liposome compositions with improved stability characteristics.
  • Technical Context: The technology involves extended-release drug delivery systems using multivesicular liposomes (MVLs), which are microscopic particles that encapsulate a drug (bupivacaine) to provide prolonged post-surgical pain relief, reducing the need for opioids.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants' submission of ANDA No. 214348 to the FDA seeking approval to market a generic version of Plaintiff's EXPAREL® drug product. The asserted patent was listed in the FDA's Orange Book on the same day it was issued and the complaint was filed.

Case Timeline

Date Event
2011-10-28 FDA approves EXPAREL® New Drug Application (NDA)
2024-05-20 ’940 Patent Priority Date
2024-12-03 U.S. Patent No. 12,156,940 issues
2024-12-03 Complaint for patent infringement filed
2044-07-02 ’940 Patent expiration date listed in the FDA Orange Book

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

  • Patent Identification: U.S. Patent No. 12,156,940, "Manufacturing of Bupivacaine Multivesicular Liposomes," issued December 3, 2024.
  • The Invention Explained:
    • Problem Addressed: The patent describes the manufacturing of bupivacaine multivesicular liposomes (MVLs) as complex and challenging, leading to batch-to-batch inconsistencies in drug release profiles ('940 Patent, Background, col. 1:21-43; Compl. ¶54-55). A critical quality control test, the in vitro release assay (IVRA), often leads to batch rejection if the product's extended-release characteristic is not stable over time (Compl. ¶55).
    • The Patented Solution: The invention is directed not to a single composition, but to batches of MVL compositions that exhibit a specific, improved stability profile. The patented solution involves a manufacturing process that yields batches with a predictable and stable drug release rate over a 12-month period, characterized by a small or slightly positive "average rate of change" in cumulative drug release at a 24-hour time point ('940 Patent, Abstract; col. 2:1-9). This contrasts with prior processes that allegedly resulted in a decreasing release rate over time, as illustrated in the patent's Figures 3A and 3B (Compl. ¶59; '940 Patent, col. 8:20-44).
    • Technical Importance: Achieving a stable, predictable release profile is critical for ensuring that an extended-release anesthetic provides consistent pain relief for its intended duration and meets the stringent quality specifications required for regulatory approval and commercial viability (Compl. ¶45, ¶55).
  • Key Claims at a Glance:
    • The complaint asserts infringement of at least independent claim 1 (Compl. ¶65, ¶74).
    • The essential elements of independent claim 1 are:
      • Batches comprising compositions of bupivacaine encapsulated multivesicular liposomes (MVLs).
      • The composition comprises bupivacaine inside internal aqueous chambers separated by lipid membranes containing specific components (DEPC, DPPG, cholesterol, tricaprylin).
      • The total bupivacaine concentration is from 12 mg/mL to 17 mg/mL.
      • The batches are manufactured within a six-month period, with each batch having a volume of about 100 to 300 liters.
      • Each batch has a cumulative percentage release of bupivacaine from 46% to 71% at a 24-hour time point, measured by a specific assay after storage for about 12 months.
      • An average rate of change in the cumulative percentage release of bupivacaine at the 24-hour time point is 0.05%/month to 0.5%/month after storage for about 12 months.
    • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

  • Product Identification: The accused products are "Jiangsu Hengrui's Proposed ANDA Products," which are proposed generic versions of EXPAREL® (bupivacaine liposome injectable suspension, 133 mg/10 mL and 266 mg/20 mL) (Compl. ¶1, fn 1).
  • Functionality and Market Context: The complaint alleges, on information and belief, that the defendants' products are purported generic versions of EXPAREL® submitted to the FDA under ANDA No. 214348 (Compl. ¶62, ¶64). As a generic equivalent, the product is expected to have the same active ingredient, dosage form, and route of administration, and to be bioequivalent to EXPAREL® (Compl. ¶1). The complaint alleges that the defendants' ANDA products will displace sales of EXPAREL®, causing injury to the plaintiffs (Compl. ¶21, ¶34). The complaint includes a cross-sectional diagram of an MVL to illustrate the general structure and release mechanism of such products (Compl. ¶53).

IV. Analysis of Infringement Allegations

  • Claim Chart Summary: The complaint alleges on "information and belief" that the defendants' proposed ANDA products will meet all limitations of at least claim 1 of the ’940 patent. The allegations are based on the premise that to be an approved generic, the defendants' product must have the same characteristics as EXPAREL®, which plaintiffs allege are covered by the patent. The complaint presents these allegations in narrative form rather than a formal chart exhibit.

’940 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Batches comprising compositions of bupivacaine encapsulated multivesicular liposomes (MVLs)... Defendants' conduct will satisfy the preamble by manufacturing batches of bupivacaine MVLs. ¶61 col. 1:46-49
...bupivacaine residing inside a plurality of internal aqueous chambers of MVLs separated by lipid membranes, wherein the lipid membranes comprise 1, 2-dierucoylphosphatidylcholine (DEPC), 1, 2-dipalmitoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DPPG) or a salt thereof, cholesterol, and tricaprylin... The proposed ANDA Products comprise compositions with bupivacaine residing in MVLs with lipid membranes containing the claimed components. ¶61 col. 1:50-54
...the total bupivacaine concentration in the composition is from 12 mg/mL to 17 mg/mL; The proposed ANDA Products comprise compositions where the total bupivacaine concentration is from 12 mg/mL to 17 mg/mL. ¶61 col. 1:57-59
...wherein the batches are manufactured within a period of six months, and each of the batches has a volume of about 100 liters to about 300 liters; The proposed ANDA Products comprise compositions where the batches are manufactured within a six-month period and have a volume of about 100 to 300 liters. ¶61 col. 1:60-62
...wherein each batch has a cumulative percentage release of bupivacaine from 46% to 71% at a 24-hour time point, measured from two to six aliquots of each batch using a rotator-facilitated in vitro release assay for at least 48 hours, after storage of the aliquots of each batch at 2°C. to 8°C. for about 12 months from batch manufacture date; The proposed ANDA Products have a cumulative percentage release of bupivacaine from 46% to 71% at the 24-hour time point, measured according to the claimed assay conditions. ¶61 col. 1:63-col.2:2
...wherein an average rate of change in the cumulative percentage release of bupivacaine of the batches at the 24-hour time point is 0.05%/month to 0.5%/month after storage of the aliquots of each batch at 2°C. to 8°C. for about 12 months. The proposed ANDA Products have an average rate of change in cumulative percentage release that is between 0.05%/month and 0.5%/month, meeting the claimed stability profile. The complaint supports this by referencing Figures 3A and 3B, which graphically depict this positive or flat slope for the new process compared to downward slopes for older processes. ¶59, ¶61 col. 2:3-9
  • Identified Points of Contention:
    • Factual Questions: The central dispute will be factual: does the defendants' manufacturing process produce batches of bupivacaine MVLs that actually meet the specific numerical limitations of claim 1? Since the complaint is based on "information and belief," discovery into the defendants' ANDA, manufacturing processes, and batch stability data will be required to substantiate these allegations.
    • Scope Questions: A potential point of contention may arise over the meaning and measurement of the "average rate of change." The claim requires a specific positive rate of change (0.05%/month to 0.5%/month). The complaint's Figures 3A and 3B illustrate this rate as a linear slope, raising the question of whether this specific calculation method is a required part of the claim.

V. Key Claim Terms for Construction

  • The Term: "average rate of change"

    • Context and Importance: This term is the central feature of the asserted independent claim and represents the core of the alleged innovation over prior art processes. The patent and complaint contrast the claimed positive or flat rate of change with the negative (downward-trending) rate of older processes (Compl. ¶59). The infringement analysis will depend entirely on whether the defendants' product batches exhibit a value within the claimed numerical range. Practitioners may focus on this term because its construction will determine the precise statistical method and data points required to prove infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim language itself does not specify the mathematical method for calculating the "rate" (e.g., linear regression, simple average). A party might argue that any scientifically valid method for determining a rate of change over the specified period that falls within the claimed range should suffice.
      • Evidence for a Narrower Interpretation: The specification provides specific examples with line charts (Figures 3A, 3B, 4A, 4B) that explicitly show a linear regression model, complete with equations like "y = 0.32x + 66.32" where the slope is the rate of change (Compl. ¶58, p. 14; '940 Patent, Fig. 3A). A party could argue that these embodiments define the term, requiring infringement to be proven using a comparable linear regression analysis over the specified time points.

  • The Term: "batches"

    • Context and Importance: The claim is directed to "batches" (plural) and requires properties that are an "average" across those batches. The construction of this term is important for determining how many batches must be assessed to prove infringement and what temporal or manufacturing relationship they must have. Practitioners may focus on this term because it defines the accused article of manufacture as a collection of products, not a single vial.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The claim states the batches are "manufactured within a period of six months," which could be argued to be the only required relationship, allowing any group of batches made in that window to qualify.
      • Evidence for a Narrower Interpretation: The patent's examples and data tables refer to specific groups of batches (e.g., "Batch Nos. 1-5 average") (Compl. p. 13, Table 1; '940 Patent, Table 1). A party might argue that "batches" implies a group manufactured under the same process and intended to be assessed together for quality control, potentially limiting the scope to defined production campaigns.

VI. Other Allegations

  • Willful Infringement: The complaint does not contain a specific count for willful infringement. However, in its prayer for relief, it requests that the case be declared exceptional under 35 U.S.C. § 285 and seeks treble damages under 35 U.S.C. § 284 (Compl. ¶¶ F, G). The factual basis for this appears to be post-suit knowledge, alleging that Defendants became aware of the ’940 patent "no later than when it was issued by the Patent Office and/or listed in the Orange Book" (Compl. ¶66).

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

  • A central issue will be one of evidentiary proof: As this is a Hatch-Waxman case filed upon patent issuance, can the plaintiff demonstrate through discovery that the defendants' proposed generic product, manufactured at commercial scale, will in fact produce "batches" that meet the specific, narrow numerical ranges for stability defined by the "average rate of change" limitation in claim 1?
  • A key legal question will be one of claim scope: How will the court construe "average rate of change"? The resolution will determine whether infringement requires a specific statistical methodology, such as the linear regression model disclosed in the patent's figures, or if other methods of calculating the rate of drug release over time could apply.
  • A final question relates to the doctrine of equivalents: Should literal infringement fail, the court may need to consider whether the stability profile of the defendants' product is equivalently stable to the claimed profile, even if it falls outside the precise numerical range of 0.05%/month to 0.5%/month. The complaint pleads infringement "either literally or under the doctrine of equivalents" (Compl. ¶65).