DCT

2:23-cv-21189

Celgene Corp v. Accord Healthcare Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:23-cv-21189, D.N.J., 10/16/2023
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant conducts substantial business in the state, is registered with the New Jersey Department of Health as a drug manufacturer, and has previously litigated patent cases in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market generic lenalidomide capsules infringes three patents covering polymorphic forms of the drug and methods of its use for treating mantle cell lymphoma.
  • Technical Context: The dispute centers on lenalidomide (marketed as Revlimid®), a critical immunomodulatory drug for treating multiple myeloma and other cancers, and specifically on the crystalline structure (polymorphism) of the active ingredient, which impacts drug stability and performance.
  • Key Procedural History: This case was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 218872 and a Paragraph IV Certification notice, which asserted that Plaintiff’s patents are invalid and/or will not be infringed. The complaint notes an extensive history of prior litigation initiated by Celgene against other generic manufacturers involving the same or related patents.

Case Timeline

Date Event
2003-09-04 ’800 and ’217 Patents Priority Date
2006-08-03 ’929 Patent Priority Date
2008-12-16 ’800 Patent Issued
2010-12-21 ’217 Patent Issued
2014-06-03 ’929 Patent Issued
2023-09-22 Accord Sent Paragraph IV Notice Letter (on or after this date)
2023-10-16 Complaint Filed

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

U.S. Patent No. 7,465,800 - “Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione”

  • Patent Identification: U.S. Patent No. 7,465,800, “Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione,” issued December 16, 2008.

The Invention Explained

  • Problem Addressed: The patent’s background section states that a single chemical compound can exist in different solid crystal forms, or polymorphs, which can have different physical properties such as solubility, stability, and bioavailability (’800 Patent, col. 1:20-30). Controlling the specific polymorphic form is critical for manufacturing a consistent and effective drug product that can meet regulatory standards (’800 Patent, col. 1:30-44).
  • The Patented Solution: The invention discloses the discovery and characterization of several distinct polymorphic forms of lenalidomide, identified as Forms A through H (’800 Patent, col. 2:5-7). By isolating and defining these specific crystalline forms, the patent provides a basis for producing a stable and consistent active pharmaceutical ingredient for use in treating diseases like cancer (’800 Patent, col. 1:45-56). The patent identifies a hemihydrated form (Form B) with a specific X-ray powder diffraction (XRPD) pattern, shown as a graph of intensity versus diffraction angle (’800 Patent, Ex. A, Fig. 6).
  • Technical Importance: Identifying and claiming specific, stable polymorphs of a blockbuster drug active ingredient is crucial for ensuring product quality, obtaining regulatory approval, and securing long-term market exclusivity.

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" but does not specify which ones (Compl. ¶28). Claim 1 is representative of the patent's core subject matter.
    • Independent Claim 1:
      • Crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate.

U.S. Patent No. 7,855,217 - “Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione”

  • Patent Identification: U.S. Patent No. 7,855,217, “Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione,” issued December 21, 2010.

The Invention Explained

  • Problem Addressed: The technical problem is identical to that of the parent ’800 Patent: the need to control the polymorphic form of lenalidomide to ensure consistent physical properties for pharmaceutical use (’217 Patent, col. 1:25-45).
  • The Patented Solution: The ’217 Patent, a divisional of the application that led to the ’800 Patent, claims solid forms of lenalidomide that are polymorphically pure to a certain degree (’217 Patent, col. 2:5-10). Specifically, it claims compositions where a particular crystalline form, the hemihydrate (Form B), constitutes the vast majority of the solid material (’217 Patent, col. 21:30-44). This ensures that the final drug product has the consistent properties of the desired polymorph.
  • Technical Importance: Claiming compositions with high polymorphic purity provides a distinct layer of patent protection beyond the polymorph itself, potentially creating a barrier to generic products that might contain mixtures of different crystalline forms.

Key Claims at a Glance

  • The complaint does not identify specific asserted claims (Compl. ¶37). Claim 1 is representative of the patent's focus on polymorphic purity.
    • Independent Claim 1:
      • A solid form of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione comprising crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione hemihydrate,
      • wherein the crystalline...hemihydrate is present at greater than about 80% by weight of the solid form.

U.S. Patent No. 8,741,929 - “Methods using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment of mantle cell lymphomas”

  • Patent Identification: U.S. Patent No. 8,741,929, “Methods using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment of mantle cell lymphomas,” issued June 3, 2014.

Technology Synopsis

  • The patent addresses the need for effective treatments for mantle cell lymphoma (MCL), a non-Hodgkin's lymphoma with a poor clinical outcome (’929 Patent, col. 2:37-41). The invention provides a specific method for treating relapsed or refractory MCL by administering lenalidomide according to a defined daily dosage and cyclical schedule (21 days of treatment followed by 7 days of rest) (’929 Patent, Abstract; col. 2:42-57).

Asserted Claims

  • The complaint does not identify specific asserted claims (Compl. ¶46). Claim 1 is a representative independent claim.

Accused Features

  • The accused feature is the future use of Accord's proposed generic lenalidomide product in accordance with its FDA-approved label, which Celgene alleges will instruct physicians and patients to practice the patented method of treating MCL (Compl. ¶¶9-10, 49).

III. The Accused Instrumentality

Product Identification

  • The accused products are Accord Healthcare, Inc.’s proposed generic lenalidomide capsules in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg dosage strengths, for which Accord seeks FDA approval via ANDA No. 218872 (Compl. ¶19).

Functionality and Market Context

  • The proposed products are generic versions of Celgene’s brand-name drug, Revlimid® (Compl. ¶1). Functionally, they are intended to deliver the active pharmaceutical ingredient lenalidomide for the treatment of cancers, including mantle cell lymphoma (Compl. ¶¶7, 9). The complaint alleges that Accord intends to manufacture, import, and sell these products in the United States prior to the expiration of the patents-in-suit (Compl. ¶19).

IV. Analysis of Infringement Allegations

The complaint, filed under the provisions of 35 U.S.C. § 271(e)(2), alleges infringement based on the submission of ANDA No. 218872 (Compl. ¶28, 37, 46). It does not provide specific factual allegations or evidence mapping elements of any asserted claims to the features of Accord's Proposed Products. Therefore, a detailed claim chart summary cannot be constructed from the complaint alone.

Identified Points of Contention

  • Technical Questions: For the ’800 and ’217 Patents, the central factual dispute will concern the physical characteristics of Accord’s ANDA product. A primary question is: What is the specific polymorphic form of the lenalidomide active ingredient contained in Accord’s proposed generic capsules, and what is its degree of purity? The case will likely depend on scientific evidence (e.g., XRPD, DSC) developed during discovery to determine if Accord's product meets the claim limitations defining Form B hemihydrate and its purity.
  • Scope Questions: For the ’929 method patent, the dispute will focus on induced infringement. A key question for the court will be whether the language of the FDA-approved label for Accord’s product will instruct or encourage medical professionals to prescribe and patients to use the drug according to the specific dosage and 28-day cycle regimen for relapsed or refractory MCL as claimed in the patent.

V. Key Claim Terms for Construction

The Term: "hemihydrate" (from ’800 Patent, Claim 1)

Context and Importance

  • The definition of this term is central to determining whether Accord's product infringes the composition claims of the ’800 Patent. The dispute may turn on whether the term requires a precise stoichiometric ratio of 0.5 water molecules per molecule of lenalidomide or if it encompasses a range of water content. Practitioners may focus on this term because the actual water content in a manufactured drug product can vary.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The parties may argue that "hemihydrate" is a generally understood term of art that does not require absolute stoichiometric precision.
  • Evidence for a Narrower Interpretation: The specification provides specific characterization data for Form B, calculating that it "loses about 3.1% volatiles up to about 175° C. (per approximately 0.46 moles of water)" and notes that "Karl Fischer water analysis also supports this conclusion" (’800 Patent, col. 7:1-5). A party could argue this data cabins the term to a narrow range around 0.5 moles of water.

The Term: "greater than about 80% by weight" (from ’217 Patent, Claim 1)

Context and Importance

  • This term of degree is critical for the infringement analysis of the ’217 Patent. The scope of "about" will determine the threshold of polymorphic purity required to infringe. If Accord's product has a purity of, for example, 78% or 79% Form B, the case could hinge on whether this falls within the scope of "about 80%."

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification defines "substantially pure" as "greater than about 80% by weight of one polymorphic form" (’217 Patent, col. 4:37-40), directly linking the claim language to this definition. The use of "about" itself suggests the patentee did not intend a strict numerical cutoff.
  • Evidence for a Narrower Interpretation: A party may argue that the scope of "about" should be constrained by the precision of the analytical techniques disclosed in the specification for measuring polymorphic purity, or by what a person of ordinary skill in the art would consider a meaningful difference in purity for pharmaceutical purposes.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges both induced and contributory infringement for all three patents-in-suit. The inducement allegations are based on the assertion that Accord, with knowledge of the patents, will encourage infringement by marketing its product with a label that instructs users to perform infringing acts (e.g., administering the drug for MCL) (Compl. ¶¶31, 40, 49). The contributory infringement allegations are based on the assertion that Accord's product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶¶32, 41, 50).

Willful Infringement

  • The complaint does not use the term "willful," but it alleges that the case is "exceptional" and requests attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶35, 44, 53). The allegation of knowledge is predicated on Accord's submission of a Paragraph IV Certification and its associated notice letter to Celgene (Compl. ¶26).

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

  • A primary issue will be one of "polymorphic identity": Can Celgene prove that the lenalidomide active ingredient in Accord's proposed generic product is, in fact, the specific crystalline "hemihydrate" form as claimed in the '800 and '217 patents, and that it meets the claimed purity threshold?
  • A key legal question will be one of "induced infringement": Will the language on the final, FDA-approved label for Accord's generic product be found to specifically instruct or encourage physicians to prescribe the drug in a manner that practices the patented dosage and cycling regimen for mantle cell lymphoma claimed in the '929 patent?
  • A central defense question, arising from the Paragraph IV certification, will be one of "validity": Can Accord demonstrate with clear and convincing evidence that the asserted claims of Celgene's patents are invalid as being anticipated or rendered obvious by the prior art that existed before the patents' priority dates?