DCT

1:20-cv-09369

Janssen Products LP v. eVenus Pharma Laboratories Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:20-cv-09369, D.N.J., 10/19/2020
  • Venue Allegations: Venue is alleged based on defendants being incorporated or having principal places of business in New Jersey, conducting continuous business in the district, or consenting to venue.
  • Core Dispute: Plaintiffs allege that Defendants' filing of Abbreviated New Drug Applications (ANDAs) to market generic versions of the cancer drug Yondelis® (trabectedin) constitutes an act of infringement of patents covering the drug's formulation and its synthetic manufacturing process.
  • Technical Context: The case concerns trabectedin, a complex antineoplastic agent derived from a marine organism, used in the treatment of certain soft tissue sarcomas and ovarian cancer.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendants’ submission of ANDAs with Paragraph IV certifications, which challenge the validity or infringement of Plaintiffs’ patents listed in the FDA’s Orange Book. The complaint alleges that Defendants have refused to produce manufacturing information related to the asserted process patent, which Plaintiffs contend is evidence that the manufacturing process is infringing.

Case Timeline

Date Event
2000-05-15 ’051 Patent Priority Date
2004-10-29 ’557 Patent Priority Date
2008-09-02 ’051 Patent Issue Date
2014-11-25 ’557 Patent Issue Date
2020-06-12 Janssen receives Paragraph IV Notice Letter from eVenus-Jiangsu
2020-06-26 Janssen receives Paragraph IV Notice Letter from Natco-Sun
2020-10-19 Complaint Filing Date

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

U.S. Patent No. 8,895,557 - Pharmaceutical Formulations of Ecteinascidin Compounds, Issued November 25, 2014

The Invention Explained

  • Problem Addressed: The patent addresses the technical challenge that the anti-cancer compound ET-743 (trabectedin) has limited aqueous solubility and is unstable in solution, which complicates the creation of a commercially viable, storable pharmaceutical product (’557 Patent, col. 2:27-42). Conventional formulations using mannitol as a bulking agent required storage at approximately -20°C and still resulted in the formation of the hydrolysis impurity ET-701 (’557 Patent, col. 3:6-15).
  • The Patented Solution: The invention provides a stable, lyophilized (freeze-dried) formulation of ET-743 by using a disaccharide, such as sucrose or lactose, as the bulking agent instead of mannitol (’557 Patent, col. 4:65-col. 5:4). This approach is described as significantly reducing the rate of degradation into the ET-701 impurity, thereby improving the product's stability and allowing for storage at higher, less burdensome temperatures like 5°C (’557 Patent, Figure 1; col. 15:52-59).
  • Technical Importance: Achieving long-term stability for a complex and otherwise unstable drug is critical for its commercial viability, simplifying the logistics of shipping, storage, and clinical administration while ensuring dose purity and patient safety (’557 Patent, col. 3:55-61).

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 3-8, 11, 14-20, 22-24, and 26 (Compl. ¶171).
  • Independent Claim 1 recites:
    • A lyophilised anti-tumor composition comprising a single active anti-tumor compound and a disaccharide selected from sucrose, lactose and a combination thereof,
    • wherein the anti-tumor compound is ET-743 and
    • wherein the disaccharide is present in a sufficient amount to inhibit conversion of the ET-743 into ET-701, such that the ET-743 composition comprises less than 2% ET-701 after storage of the ET-743 composition at 5° C. for 3 months.
  • The complaint reserves the right to assert additional claims.

U.S. Patent No. 7,420,051 - Synthetic Process for the Manufacture of an Ecteinascidin Compound, Issued September 2, 2008

The Invention Explained

  • Problem Addressed: The patent describes that prior methods for producing ecteinascidin compounds were either low-yield extractions from natural marine sources or involved long and complicated synthetic pathways, creating a need for more economical and efficient manufacturing processes (’051 Patent, col. 2:20-30; col. 10:41-49).
  • The Patented Solution: The patent discloses novel and more efficient synthetic and semi-synthetic routes for manufacturing ecteinascidin compounds and their intermediates (’051 Patent, Abstract). The invention details specific chemical transformations, such as processes to create the core fused-ring structure of the molecule, starting from more accessible precursor compounds like cyanosafracin B (’051 Patent, col. 10:50-col. 11:2; col. 68:42-55). The detailed description provides multiple alternative reaction schemes to build the complex molecule (’051 Patent, Schemes 1-VIII).
  • Technical Importance: The development of a viable, large-scale synthetic process is a critical step in transforming a rare natural product into a commercially available pharmaceutical drug, enabling consistent supply for clinical use and further research (’051 Patent, col. 42:25-29).

Key Claims at a Glance

  • The complaint asserts claims 7, 11, and 14 (Compl. ¶191). These claims depend from independent process claims 5, 9, and 12, respectively.
  • Independent Claim 12, on which asserted claim 14 depends, recites:
    • A process for the manufacture of an ecteinascidin compound,
    • wherein the process comprises converting stereospecifically an α-ketolactone of formula (36) to a spiroisoquinoline compound Et770,
    • in accordance with the following scheme: [a multi-step chemical reaction diagram is provided].
  • The complaint reserves the right to assert additional claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the proposed generic drug products detailed in Abbreviated New Drug Application (ANDA) No. 214327, filed by the eVenus-Jiangsu-Fresenius defendants, and ANDA No. 214837, filed by the Natco-Sun defendants (Compl. ¶¶2-3).

Functionality and Market Context

  • The ANDA products are proposed generic versions of Plaintiffs' Yondelis® (trabectedin) 1 mg/vial, an injectable lyophilized powder (Compl. ¶¶2-3). Under the Hatch-Waxman Act, the filing of an ANDA seeking approval to market a generic version of a branded drug before the expiration of relevant patents is a statutory act of infringement that allows the patent holder to initiate litigation (Compl. ¶¶169, 198).
  • Plaintiffs allege their Yondelis® product is "highly successful" and that the defendants' generic products, if approved, would displace sales and cause injury (Compl. ¶¶2, 51).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’557 Patent Infringement Allegations

The complaint alleges that the defendants do not dispute that their proposed ANDA products infringe numerous claims of the ’557 Patent, including claim 1 (Compl. ¶¶132, 160). The infringement allegation is based on the defendants’ submission of their ANDAs, which describe drug products that allegedly embody the patented formulation.

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A lyophilised anti-tumor composition... The proposed generic products are lyophilized (freeze-dried) formulations of trabectedin. ¶¶2, 170 col. 2:19-21
...comprising a single active anti-tumor compound... wherein the anti-tumor compound is ET-743... The proposed ANDA products are identified as containing trabectedin (also known as ET-743) as the active pharmaceutical ingredient. ¶¶2-3 col. 1:44-51
...and a disaccharide selected from sucrose, lactose and a combination thereof... The complaint alleges on information and belief that the defendants "copied the inventions of the '557 Patent" by using a claimed disaccharide to achieve the necessary stability for their formulation. ¶¶131, 159 col. 5:1-4
...wherein the disaccharide is present in a sufficient amount to inhibit conversion of the ET-743 into ET-701, such that the ET-743 composition comprises less than 2% ET-701 after storage of the ET-743 composition at 5° C. for 3 months. The allegation of copying the "highly successful and advantageous" commercial formulation implies that the defendants' products achieve this claimed functional stability threshold. ¶¶131, 159 col. 5:17-25
  • Identified Points of Contention:
    • Validity Question: The primary dispute concerning the ’557 Patent appears to be validity, not infringement. The complaint states that the defendants' Paragraph IV letters assert that the claims of the ’557 Patent are invalid as obvious (Compl. ¶¶128, 157). The central issue for the court will therefore likely be whether substituting a disaccharide for mannitol to achieve superior stability would have been obvious to a person of ordinary skill in the art at the time of the invention.

’051 Patent Infringement Allegations

The complaint does not provide a detailed mapping of the defendants' manufacturing process to the claims of the ’051 Patent. Instead, it advances an infringement theory based on inference. The complaint alleges, on information and belief, that the defendants will use the patented process to manufacture the trabectedin API for their generic products (Compl. ¶¶107, 112, 119). This belief is allegedly supported by the defendants’ refusal to provide Plaintiffs with manufacturing information, such as Drug Master Files (DMFs) and batch records, during pre-suit communications (Compl. ¶¶115-118, 145-148). Plaintiffs argue this refusal is "consistent with the conclusion that the commercial processes... protected by the '051 Patent will be used" (Compl. ¶¶119, 149).

  • Identified Points of Contention:
    • Evidentiary Question: The primary issue for the ’051 Patent is factual and will depend entirely on evidence produced during discovery. The key question for the court will be whether the manufacturing process actually used or planned by the defendants falls within the scope of the asserted process claims. The sufficiency of the complaint's allegations, based on an adverse inference from pre-suit conduct, may be tested at the pleading stage.

V. Key Claim Terms for Construction

For the ’557 Patent

  • The Term: "a sufficient amount to inhibit conversion ... such that the ET-743 composition comprises less than 2% ET-701 after storage of the ET-743 composition at 5° C. for 3 months" (from Claim 1).
  • Context and Importance: This is a functional limitation that defines the required stability of the claimed formulation. Its construction is critical for the obviousness analysis, as the central question of validity will turn on whether achieving this specific, quantitative level of stability was taught or suggested by the prior art.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim language is results-oriented and not tied to a specific ratio of drug to disaccharide. Plaintiffs may argue that any formulation using a claimed disaccharide that achieves the "<2% ET-701 after 3 months" result infringes, regardless of the precise ratio used. The patent's specification teaches that disaccharides generally provide this stabilizing effect (’557 Patent, col. 5:1-16).
    • Evidence for a Narrower Interpretation: Defendants may argue the term should be understood in the context of the specific embodiments disclosed. The patent's examples demonstrate this stability using specific drug-to-excipient ratios (e.g., 0.250 mg ET-743 to 500 mg sucrose/lactose) (’557 Patent, Tables II-IV). They might contend that the claimed functional result is tied to these exemplified parameters.

For the ’051 Patent

  • The complaint does not provide sufficient detail for analysis of key claim terms, as the infringement allegation is based on inference rather than a specific comparison of the accused process to the claim language. The dispute at this stage is factual (what is the process?) rather than legal (what does a claim term mean?).

VI. Other Allegations

  • Indirect Infringement: The complaint includes allegations of future contributory and induced infringement for both patents, which would occur upon FDA approval and commercial launch of the defendants' products (Compl. ¶¶170, 180). This is based on the expected sale and marketing of the generic products with instructions for their use, which would allegedly induce physicians and patients to infringe.
  • Willful Infringement: Willfulness is alleged for both patents, based on defendants' purported knowledge prior to their ANDA filings (Compl. ¶¶193, 220). For the ’557 Patent, this knowledge is predicated on its listing in the FDA Orange Book (Compl. ¶97) and the defendants' own Paragraph IV notice letters acknowledging the patent (Compl. ¶¶172, 201). For the ’051 Patent, willfulness is alleged based on actual and constructive notice and the defendants' alleged copying of the patented process (Compl. ¶¶163, 219).

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

  • A core issue will be one of validity: Can the defendants demonstrate by clear and convincing evidence that the '557 Patent’s formulation—specifically, the use of a disaccharide like sucrose to achieve a specific, quantitative improvement in the stability of trabectedin—was obvious over the prior art available to a formulator at the time?
  • A key evidentiary question will be one of process identification: For the '051 Patent, will discovery confirm the plaintiffs’ inferred allegation that the defendants’ manufacturing process for the trabectedin API infringes the asserted process claims, or will the evidence show a non-infringing, "designed-around" synthesis route?