DCT

1:24-cv-08723

Ipsen Biopharma Inc v. Conjupro BioTherap Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-08723, D.N.J., 08/23/2024
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Conjupro has a regular and established place of business in the district, and the other foreign-based defendants have allegedly committed acts of infringement in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of a New Drug Application to the FDA for a generic irinotecan liposome injection product constitutes an act of patent infringement.
  • Technical Context: The technology concerns stabilizing pharmaceutical compositions of camptothecin-based cancer drugs, like irinotecan, by encapsulating them in liposomes to improve shelf-life and stability.
  • Key Procedural History: The complaint notes a related, prior-filed case between the same parties in the same district, Ipsen Biopharmaceuticals, Inc., et al. v. Conjupro Biotherapeutics, Inc., et al., Civil Action No. 24-4991, suggesting an ongoing dispute over generic versions of Plaintiff's products. The patent-in-suit is subject to a terminal disclaimer over a parent patent, which may limit its enforceable term.

Case Timeline

Date Event
2014-11-17 FDA grants fast track designation for Plaintiff's Onivyde® product
2015-10-16 Earliest Priority Date for U.S. Patent No. 12,059,497
2015-10-22 FDA approves Plaintiff's NDA for Onivyde® (irinotecan liposome injection)
2024-08-13 U.S. Patent No. 12,059,497 Issues
2024-08-23 Complaint Filed

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

  • Patent Identification: U.S. Patent No. 12,059,497, “Stabilizing Camptothecin Pharmaceutical Compositions,” issued August 13, 2024 (’497 Patent).

The Invention Explained

  • Problem Addressed: The patent background describes how pharmaceutical compositions of camptothecin drugs encapsulated in liposomes (lipid spheres) suffer from instability. Specifically, the phospholipids that form the liposome structure can hydrolyze, or break down, into a substance called lyso-phosphatidylcholine (lyso-PC). This degradation compromises the liposome's integrity and can alter the release of the encapsulated drug, affecting its stability and therapeutic performance. This instability is sensitive to the pH of the composition. (’497 Patent, col. 1:36-53).
  • The Patented Solution: The invention provides a more stable liposomal formulation for camptothecin compounds like irinotecan. The solution involves carefully controlling several manufacturing parameters in synergy: the ratio of the drug to the phospholipid, the pH of the final preparation, the amount of a "trapping agent" (e.g., sucrose octasulfate) used to hold the drug inside the liposome, and the amount of the trapping agent's counter-ion. (’497 Patent, col. 2:21-43). By optimizing these factors, the patented compositions are designed to generate significantly less lyso-PC during refrigerated storage, thereby improving shelf-life and product robustness. (’497 Patent, col. 2:43-54; FIG. 1A).
  • Technical Importance: This approach allows for the creation of a shelf-stable, injectable liposomal cancer therapy, ensuring that the drug maintains its intended structure and release characteristics from manufacture through administration to a patient. (’497 Patent, col. 2:9-19).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specifying which claims will be asserted (Compl. ¶37). Independent claim 1 is representative:
  • A storage stabilized liposomal irinotecan composition comprising cholesterol, one or more phospholipids, and irinotecan sucrose octasulfate (SOS) encapsulated in unilamellar liposomes, said composition having:
    • an irinotecan:total phospholipids ratio corresponding to a total of 500 grams±10% by weight irinotecan moiety per mol of total phospholipids;
    • a gram-equivalent ratio of from 0.85 to 1.2, as determined by the molar amounts of co-encapsulated irinotecan and sucrose octasulfate;
    • a pH before storage of from about 7.25 to about 7.5 at room temperature; and
    • wherein, after the first 6 months storage of said composition at a storage temperature of from 2-8° C., there is less than 20 mol % lyso-phosphatidylcholine ("lyso-PC"), relative to the total phospholipids.
  • The complaint implicitly reserves the right to assert additional independent and dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused product is an irinotecan liposome injection product described in New Drug Application (“NDA”) No. 218923, referred to as the "Proposed Conjupro Product" (Compl. ¶15, ¶20).

Functionality and Market Context

  • The Proposed Conjupro Product is alleged to be a generic pharmaceutical version of Plaintiff’s branded drug, Onivyde® (Compl. ¶6, ¶29). Onivyde® is an injectable liposomal formulation of irinotecan indicated for the treatment of metastatic adenocarcinoma of the pancreas (Compl. ¶29, ¶31). The complaint alleges that Defendants submitted the NDA to seek FDA approval for commercial manufacture, use, and sale of this generic version in the United States prior to the expiration of the ’497 Patent (Compl. ¶33). The complaint does not provide specific technical details of the accused product's formulation, instead alleging that it "meets or embodies all elements of one or more claims of the patent-in-suit" (Compl. ¶34).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges infringement under 35 U.S.C. § 271(e)(2)(A) based on the submission of the Conjupro NDA (Compl. ¶36). It does not contain an element-by-element claim chart. The narrative theory is that Defendants' proposed generic product is a copy of Plaintiff's Onivyde® product, and that the composition of Onivyde® is covered by the claims of the ’497 patent (Compl. ¶32). Therefore, the act of seeking FDA approval to market the generic product is an act of infringement. The following chart summarizes the allegations based on this theory.

’497 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A storage stabilized liposomal irinotecan composition comprising cholesterol, one or more phospholipids, and irinotecan sucrose octasulfate (SOS) encapsulated in unilamellar liposomes... The Proposed Conjupro Product is alleged to be a liposomal irinotecan composition that meets or embodies all elements of the claims. ¶34, ¶37 col. 2:43-54
...an irinotecan:total phospholipids ratio corresponding to a total of 500 grams±10% by weight irinotecan moiety per mol of total phospholipids... The Proposed Conjupro Product is alleged to contain the claimed ratio of irinotecan to phospholipids. ¶34, ¶37 col. 4:50-54
...a gram-equivalent ratio of from 0.85 to 1.2, as determined by the molar amounts of co-encapsulated irinotecan and sucrose octasulfate... The Proposed Conjupro Product is alleged to have the claimed gram-equivalent ratio of irinotecan to the trapping agent. ¶34, ¶37 col. 13:29-35
...a pH before storage of from about 7.25 to about 7.5 at room temperature... The Proposed Conjupro Product is alleged to be formulated at the claimed pH level. ¶34, ¶37 col. 4:3-5
...wherein, after the first 6 months storage... at... 2-8° C., there is less than 20 mol % lyso-phosphatidylcholine ("lyso-PC"), relative to the total phospholipids. The Proposed Conjupro Product is alleged to exhibit the claimed stability profile, with lyso-PC formation remaining below the claimed threshold during storage. ¶34, ¶37 col. 2:45-49
  • Identified Points of Contention:
    • Scope Questions: A central dispute may revolve around the construction of the claim limitations that define the composition's stability and component ratios. For example, the methodology for measuring the "gram-equivalent ratio" and "mol % lyso-PC" could become a point of contention if different testing methods yield different results.
    • Technical Questions: The primary technical question for the court will be whether the specific formulation detailed in Defendants' confidential NDA filing actually falls within the scope of the asserted claims. The complaint does not provide sufficient detail for analysis of the accused product's specific formulation, but this will be a central issue as the case proceeds through discovery.

V. Key Claim Terms for Construction

  • The Term: "storage stabilized"

  • Context and Importance: This term appears in the preamble of claim 1 and sets the context for the invention. Practitioners may focus on this term because its definition is tied to the quantitative stability limitation later in the claim ("less than 20 mol % lyso-PC after... 6 months storage"). The dispute will likely center on whether this term imparts a separate, qualitative limitation on stability beyond the explicit numerical threshold or is simply defined by it.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent's summary states the invention provides compositions with "improved stability" and "reduced rates of formation of lyso-phospholipid" generally, which could support an interpretation that "storage stabilized" is a broad descriptor of the overall goal. (’497 Patent, col. 2:21-26).
    • Evidence for a Narrower Interpretation: The specification repeatedly links stability to specific, measured outcomes, such as forming "not more than 20 mol % of lyso-PL... during storage for the first 6 months," which could support construing "storage stabilized" as being defined by meeting that specific numerical limitation. (’497 Patent, col. 2:45-49).

  • The Term: "gram-equivalent ratio"

  • Context and Importance: This term defines a key relationship between the active drug and the trapping agent within the liposome. Practitioners may focus on this term because infringement will depend on precise chemical analysis. The definition of how this ratio is "determined" could be critical if the parties' experts use different analytical techniques.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent provides a general definition of the ratio in the claims. A party might argue that any scientifically valid method for determining the molar amounts of the components should suffice.
    • Evidence for a Narrower Interpretation: The patent's detailed description provides a specific formula for calculating an "ER" (Equivalent Ratio) based on molar amounts of irinotecan and the sulfate compound (’497 Patent, col. 13:15-24). A party could argue that this specific formula and the methods described in the examples for measuring its inputs define the proper way to "determine" the ratio.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that the commercial manufacture, use, sale, or importation of the Proposed Conjupro Product will induce and/or contribute to infringement (Compl. ¶39). This allegation is likely premised on the eventual sale of the product with a label instructing medical professionals and patients to use it in a manner covered by the patent's claims.
  • Willful Infringement: The complaint does not use the word "willful" but alleges that Defendants are "aware of the existence of the ’59,497 patent" and that filing the NDA constitutes an act of infringement (Compl. ¶43). This allegation of knowledge, coupled with the request for a finding that the case is "exceptional" and for an award of attorneys' fees, lays the groundwork for a potential willfulness claim (Compl. ¶44).

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

  • A core issue will be one of claim construction and measurement: How will the court define the specific quantitative thresholds required by the claims, such as the "gram-equivalent ratio" and the maximum "mol % lyso-PC," and what analytical methods will be deemed appropriate for determining whether the accused product meets these precise chemical and stability criteria?
  • A key evidentiary question will be one of ANDA composition: What will discovery of Defendants' confidential NDA filing reveal about the exact formulation, manufacturing process, and stability data for the Proposed Conjupro Product, and does this evidence demonstrate that the proposed generic product will, in fact, possess all the characteristics required by the asserted patent claims?