DCT

1:24-cv-04991

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-04991, D.N.J., 04/15/2024
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Conjupro Biotherapeutics, Inc. maintains its principal place of business in the district, and the foreign defendants are not residents of the United States.
  • Core Dispute: Plaintiff alleges that Defendants' submission of a New Drug Application to the FDA for a generic irinotecan liposome injection product constitutes infringement of eight patents covering the branded drug Onivyde®, including patents on the drug's liposomal composition and its use in treating pancreatic cancer.
  • Technical Context: The dispute centers on liposomal drug delivery, a technology used to encapsulate chemotherapy agents to improve their stability, delivery to tumor sites, and therapeutic profile.
  • Key Procedural History: This is a Hatch-Waxman action initiated after Defendants filed a New Drug Application (NDA) with a Paragraph IV certification, challenging patents listed in the FDA's "Orange Book" for Plaintiff's branded drug, Onivyde®. Plaintiff filed this complaint within the 45-day statutory window following receipt of Defendants' notice letter, triggering an automatic 30-month stay of FDA approval for the generic product.

Case Timeline

Date Event
2004-05-03 U.S. Patent No. 8,329,213 Priority Date
2012-06-13 Patent Family Priority Date ('497', '473', '162', '442', '724', '795', '597')
2012-12-11 U.S. Patent No. 8,329,213 Issued
2014-11-17 FDA grants fast track designation for Onivyde® investigation
2015-10-22 FDA approves Plaintiff's Onivyde® (irinotecan liposome injection)
2016-05-17 U.S. Patent No. 9,339,497 Issued
2016-06-14 U.S. Patent No. 9,364,473 Issued
2016-09-27 U.S. Patent No. 9,452,162 Issued
2016-11-15 U.S. Patent No. 9,492,442 Issued
2017-08-01 U.S. Patent No. 9,717,724 Issued
2021-04-20 U.S. Patent No. 10,980,795 Issued
2022-06-28 U.S. Patent No. 11,369,597 Issued
2024-03-05 Plaintiff receives notice of Defendant's NDA and PIV Certification (on or after this date)
2024-04-15 Complaint Filing Date

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

U.S. Patent No. 8,329,213 - “Liposomes Useful For Drug Delivery,” issued December 11, 2012

The Invention Explained

  • Problem Addressed: The patent describes the general challenge of effectively delivering therapeutic compounds to target sites in vivo, a process for which liposomes (lipid bilayer vesicles) are often used as carriers (Compl. ¶27; '213' Patent, col. 1:16-22).
  • The Patented Solution: The invention provides a specific liposome composition where a drug entity is loaded and retained using a combination of a substituted ammonium compound and a polyanion within the liposome's interior. The specification highlights the use of sucrose octasulfate as a polyanion to form a stable, precipitated salt with a drug like irinotecan inside the liposome ('213 Patent, Abstract; col. 10:48-54).
  • Technical Importance: This approach provides a method for achieving high-efficiency loading and stable retention of certain drugs within liposomes, potentially improving their circulation time and therapeutic index ('213 Patent, col. 22:5-14).

Key Claims at a Glance

  • The complaint does not identify specific asserted claims, alleging infringement of "one or more claims" (Compl. ¶46). Independent claim 11 is representative of the core composition claims.
  • Essential elements of Independent Claim 11:
    • A composition comprising a liposome having an interior space.
    • Wherein said interior space is an interior aqueous space containing a sucrose octasulfate salt of irinotecan.
    • And is encapsulated by a membrane comprising one or more lipids.
  • The complaint generally alleges infringement of the patent and does not explicitly reserve rights to assert dependent claims (Compl. ¶46).

U.S. Patent No. 9,339,497 - “Methods For Treating Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan,” issued May 17, 2016

The Invention Explained

  • Problem Addressed: The patent background notes that pancreatic cancer has a "dismal prognosis" and that there is an "urgent need for improvements in, and effective alternatives to, current therapies" ('497 Patent, col. 2:41-45).
  • The Patented Solution: The invention claims a specific method for treating metastatic pancreatic cancer that has progressed after gemcitabine-based therapy. The solution is a defined combination therapy regimen comprising specific doses of liposomal irinotecan, 5-fluorouracil (5-FU), and leucovorin administered on a two-week cycle ('497 Patent, Abstract; col. 3:11-23). This regimen corresponds to a clinical trial design detailed in related patents ('795 Patent, Fig. 7).
  • Technical Importance: The patent claims a specific, clinically evaluated treatment protocol that provides a new therapeutic option for patients with an advanced and difficult-to-treat cancer ('497 Patent, col. 2:41-45).

Key Claims at a Glance

  • The complaint does not identify specific asserted claims, alleging infringement of "one or more claims" (Compl. ¶56). Independent claim 1 is representative of the core method claims.
  • Essential elements of Independent Claim 1:
    • A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has previously been treated with gemcitabine.
    • Comprising intravenously administering an antineoplastic therapy once every two weeks.
    • The therapy consists of 80 mg/m² of MM-398 liposomal irinotecan, 200 mg/m² of (l)-form of leucovorin or 400 mg/m² of (l+d) racemic form of leucovorin, and 2,400 mg/m² of 5-fluorouracil.
    • Where no other antineoplastic agent is administered.
  • The complaint generally alleges infringement of the patent and does not explicitly reserve rights to assert dependent claims (Compl. ¶56).

Additional Patents-in-Suit: Multi-Patent Capsules

  • U.S. Patent No. 9,364,473: Titled “Methods For Treating Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan,” issued June 14, 2016.

    • Technology Synopsis: This patent, part of the same family as the ’497 Patent, addresses the need for effective pancreatic cancer treatments. It claims a method of co-administering liposomal irinotecan, 5-fluorouracil, and leucovorin on a two-week cycle, specifying particular dosages and administration sequences.
    • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶66).
    • Accused Features: The accused features are the manufacture, use, and sale of the Proposed Conjupro Product, whose label will allegedly instruct for its use in the patented method (Compl. ¶66, ¶68).

  • U.S. Patent No. 9,452,162: Titled “Methods For Treating Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan,” issued September 27, 2016.

    • Technology Synopsis: Also from the ’497 Patent family, this patent covers methods for treating pancreatic cancer. It claims a combination therapy regimen involving liposomal irinotecan, 5-fluorouracil, and leucovorin, with specific claim language directed to particular patient populations and dosage adjustments.
    • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶76).
    • Accused Features: The manufacture, use, and sale of the Proposed Conjupro Product for the treatment of pancreatic cancer (Compl. ¶76, ¶78).

  • U.S. Patent No. 9,492,442: Titled “Methods For Treating Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan,” issued November 15, 2016.

    • Technology Synopsis: Another member of the ’497 Patent family, this patent claims methods of treating pancreatic cancer with a combination therapy of liposomal irinotecan, 5-fluorouracil, and leucovorin, including claims directed to patients with specific genetic markers (UGT1A1*28 allele).
    • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶86).
    • Accused Features: The Proposed Conjupro Product and its intended method of use (Compl. ¶86, ¶88).

  • U.S. Patent No. 9,717,724: Titled “Methods For Treating Pancreatic Cancer Using Combination Therapies,” issued August 1, 2017.

    • Technology Synopsis: Continuing the same patent family, this patent claims methods of treating pancreatic cancer with liposomal irinotecan. The claims cover specific administration protocols, including intravenous infusion times for the combination therapy components.
    • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶96).
    • Accused Features: The Proposed Conjupro Product and its intended administration instructions (Compl. ¶96, ¶98).

  • U.S. Patent No. 10,980,795: Titled “Methods For Treating Pancreatic Cancer Using Combination Therapies Comprising Liposomal Irinotecan,” issued April 20, 2021.

    • Technology Synopsis: A further patent in the ’497 family, this patent claims methods of treating metastatic adenocarcinoma of the pancreas after progression on gemcitabine. The claims specify a two-week cycle of liposomal irinotecan, 5-fluorouracil, and leucovorin with specific dosages.
    • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶106).
    • Accused Features: The Proposed Conjupro Product and its intended use for treating pancreatic cancer as described in its NDA (Compl. ¶106, ¶108).

  • U.S. Patent No. 11,369,597: Titled “Methods For Treating Pancreatic Cancer Using Combination Therapies,” issued June 28, 2022.

    • Technology Synopsis: The most recent patent asserted from the ’497 family, this patent also claims methods of treating pancreatic cancer. The claims are directed to specific patient populations and dosage regimens for the liposomal irinotecan combination therapy.
    • Asserted Claims: The complaint asserts "one or more claims" (Compl. ¶116).
    • Accused Features: The Proposed Conjupro Product and its intended therapeutic use (Compl. ¶116, ¶118).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Proposed Conjupro Product," identified as an "irinotecan liposome injection product" that is the subject of Defendants' New Drug Application (NDA) No. 218923 (Compl. ¶15, ¶20).

Functionality and Market Context

  • The complaint alleges that the Proposed Conjupro Product is a generic version of Plaintiff's branded drug, Onivyde® (irinotecan liposome injection), for which Defendants seek FDA approval to commercially manufacture, use, and sell in the United States (Compl. ¶6, ¶35, ¶39). The product is intended for intravenous use in treating cancer, and the complaint alleges it embodies the compositions claimed in the patents-in-suit and that its proposed labeling will instruct for the methods of use claimed in the patents-in-suit (Compl. ¶42, ¶58).
    No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not specify which claims of the patents-in-suit are asserted, nor does it provide claim charts or detailed infringement theories. The following summaries are based on representative independent claims and the complaint's general allegations that the Proposed Conjupro Product will infringe.

8,329,213 Patent Infringement Allegations

Claim Element (from Independent Claim 11) Alleged Infringing Functionality Complaint Citation Patent Citation
A composition comprising a liposome having an interior space, wherein said interior space: The complaint alleges the Proposed Conjupro Product is a liposomal irinotecan formulation. ¶20, ¶42 col. 2:50-53
1) is an interior aqueous space containing a sucrose octasulfate salt of irinotecan, and The complaint alleges the product embodies the claimed composition. ¶42, ¶46 col. 10:48-54
2) is encapsulated by a membrane comprising one or more lipids. The complaint alleges the product is a liposomal formulation. ¶20, ¶42 col. 1:24-34

9,339,497 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating metastatic adenocarcinoma of the pancreas in a human patient who has previously been treated with gemcitabine, The complaint alleges Defendants' product is a generic version of Onivyde®, which is indicated for this patient population, suggesting the product's label will instruct this use. ¶37, ¶56, ¶58 col. 2:20-25
comprising intravenously administering an antineoplastic therapy once every two weeks, The complaint alleges the product's use will infringe, suggesting the label will instruct a two-week cycle consistent with the Onivyde® regimen. ¶42, ¶56 col. 3:7-14
the therapy consisting of: 80 mg/m² of MM-398 liposomal irinotecan, The complaint alleges the product will be administered at a dose that infringes the patent. ¶42, ¶56 col. 3:14-16
200 mg/m² of the (l) form of leucovorin or 400 mg/m² of the (l+d) racemic form of leucovorin, and 2,400 mg/m² of 5-fluorouracil, The complaint alleges the product will be used in a combination therapy that infringes the patent. ¶37, ¶56 col. 3:17-21
where no other antineoplastic agent is administered. The infringement allegation implies the proposed label will not include other antineoplastic agents for this specific regimen. ¶42, ¶56 col. 3:21-23
  • Identified Points of Contention:
    • Scope Questions: For the '213 Patent, a key question may be whether the term "sucrose octasulfate salt of irinotecan" can be construed to read on the specific formulation used in the Proposed Conjupro Product, particularly if Defendants employ a different but functionally similar stabilizing agent. For the '497 Patent and related method patents, a central issue will be whether the product's final approved label instructs or encourages administration in a manner that meets every limitation of the claimed method, including dosage, timing, and the exclusion of other agents.
    • Technical Questions: A primary technical question will be one of formulation equivalence: does the accused generic product contain the same components and exhibit the same structural and release characteristics as the composition defined in the '213 Patent claims? The complaint does not provide sufficient detail for analysis of the specific formulation of the Proposed Conjupro Product.

V. Key Claim Terms for Construction

  • The Term: "sucrose octasulfate salt of irinotecan" ('213 Patent, Claim 11)

    • Context and Importance: This term defines the core chemical composition that allegedly provides stability to the encapsulated drug. Practitioners may focus on this term because the infringement dispute for the '213 Patent will likely depend on whether the Defendants' formulation falls within its scope, either literally or under the doctrine of equivalents. Defendants may argue their product uses a different, non-infringing stabilization mechanism.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The '213 Patent specification discusses the invention in the broader context of using a "polyanion," which could suggest that "sucrose octasulfate" is one example of a broader class of stabilizing agents ('213 Patent, col. 2:51).
      • Evidence for a Narrower Interpretation: The claim explicitly recites "sucrose octasulfate." The detailed description and examples may repeatedly emphasize this specific compound as the key to the invention, potentially supporting a narrower construction limited to that specific salt ('213 Patent, col. 10:48-54).

  • The Term: "co-administering" ('497 Patent, Claim 1, in related patents) and administration sequence ("wherein the MM-398 liposomal irinotecan is administered prior to the leucovorin and the leucovorin is administered prior to the 5-FU")

    • Context and Importance: The sequence and timing of drug administration are critical limitations in the asserted method claims. Practitioners may focus on these terms because Defendants could argue that their proposed product label allows for a different, non-infringing sequence of administration or does not require the specific timing that would constitute infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The term "co-administering" is sometimes used broadly in the art to mean administration during the same overall course of therapy.
      • Evidence for a Narrower Interpretation: The claims of related patents and the specification's description of the clinical trial protocol provide a highly specific sequence and timing for administering the three drugs ('795 Patent, col. 3:23-27; Fig. 7). This intrinsic evidence may support a narrow construction requiring the drugs to be given in a specific order during a single treatment session.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement for all asserted patents (e.g., Compl. ¶48, ¶58). The basis for this allegation is Defendants' filing of an NDA that, upon approval, would result in a product label instructing medical professionals and patients to use the infringing composition in the infringing manner for treating pancreatic cancer (Compl. ¶39, ¶42).
  • Willful Infringement: The complaint does not use the term "willful infringement" but alleges that Defendants were "aware of the existence" of the patents-in-suit (e.g., Compl. ¶52, ¶62). This awareness is predicated on the patents' listing in the FDA Orange Book for Onivyde® and Defendants' submission of a Paragraph IV Certification acknowledging the patents. The complaint also asserts that this is an "exceptional case" to seek attorneys' fees under 35 U.S.C. § 285 (e.g., Compl. ¶53, ¶63).

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

  • A core issue will be one of formulation equivalence: does the chemical composition of the accused generic product, particularly the mechanism used to stabilize irinotecan within its liposomes, fall within the literal scope of the asserted composition claims, or will the dispute center on technical arguments of equivalence?
  • A key evidentiary question will be one of induced infringement: will the final FDA-approved product label for the accused generic drug contain explicit instructions or recommendations that encourage physicians to prescribe and administer the drug in a manner that practices every step of the asserted method claims, including the specific dosages, patient population, and sequence of administration?