Celgene Corp v. Deva Holding As

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Celgene Corporation (Delaware)
  • Defendant: Deva Holding A.S. (Turkey)
  • Plaintiff’s Counsel: Saul Ewing LLP
• Case Identification: 2:23-cv-02992, D.N.J., 05/31/2023
• Venue Allegations: Venue is alleged to be proper because the defendant is a foreign corporation and may be sued in any judicial district.
• Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for generic versions of the cancer drug Revlimid® constitutes an act of infringement of two patents covering specific polymorphic forms of the active ingredient, lenalidomide.
• Technical Context: The case centers on polymorphism, a phenomenon where a single chemical compound can exist in multiple crystalline solid-state forms, each with distinct physical properties like stability and solubility that are critical for pharmaceutical manufacturing and clinical performance.
• Key Procedural History: The complaint’s certification of related cases indicates that Plaintiff has engaged in extensive prior litigation against numerous other generic drug manufacturers concerning patents covering Revlimid®, suggesting a well-established and aggressive patent enforcement strategy.

Case Timeline

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. 7465800, "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 notes that different solid crystal forms, or polymorphs, of a drug compound can exhibit different physical and chemical properties, such as solubility and stability, which can affect the safety and efficacy of a drug product (ʼ800 Patent, col. 1:21-44). Discovering and characterizing new, stable polymorphs is therefore a critical step in pharmaceutical development.
  • The Patented Solution: The invention discloses the discovery and characterization of several new polymorphic forms of the compound lenalidomide, identified as Forms A through H, along with methods for their preparation (’800 Patent, Abstract; col. 2:60-65). The patent provides detailed analytical data, including X-ray powder diffraction (XRPD) patterns and differential scanning calorimetry (DSC) thermograms, to define the distinct physical properties of each form (’800 Patent, Figs. 1-31).
  • Technical Importance: Identifying and claiming specific, stable polymorphic forms of an active pharmaceutical ingredient allows for the development of drug products with consistent manufacturing characteristics and predictable clinical performance.
• Key Claims at a Glance:
  • The complaint alleges infringement of one or more unspecified claims (Compl. ¶21). Independent claim 1 is representative:
  • 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. 7855217, "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: As a divisional of the application leading to the ’800 Patent, the ’217 patent addresses the same technical problem: the need to identify and characterize distinct, stable crystalline forms of lenalidomide for use in pharmaceutical products (’217 Patent, col. 2:22-47).
  • The Patented Solution: The invention claims solid forms of lenalidomide that contain the specific crystalline hemihydrate form (disclosed as "Form B" in the specification) at specified levels of purity (’217 Patent, col. 2:1-9). This provides a way to claim not just the polymorph itself, but also pharmaceutical compositions that are substantially composed of that specific polymorph.
  • Technical Importance: Claiming compositions with a high percentage of a specific polymorph is important for ensuring that a drug product is not only effective but also stable and free from less desirable or uncharacterized crystalline forms.
• Key Claims at a Glance:
  • The complaint alleges infringement of one or more unspecified claims (Compl. ¶30). Independent claim 1 is representative:
  • 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.

III. The Accused Instrumentality

Product Identification

• Defendant’s proposed generic lenalidomide capsules in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg strengths, for which Defendant submitted ANDA No. 217554 to the FDA ("Deva's Proposed Products") (Compl. ¶1, ¶12).

Functionality and Market Context

• Deva's Proposed Products are alleged to be generic versions of Celgene’s Revlimid® drug product, which contains the active ingredient lenalidomide (Compl. ¶1, ¶6). Revlimid® is a significant cancer therapy, and the complaint alleges Deva seeks to market its generic versions prior to the expiration of the patents-in-suit (Compl. ¶1). The functionality of the accused products is to deliver a therapeutically effective dose of lenalidomide to patients.

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint alleges that Defendant’s submission of its ANDA constitutes a technical act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶21, ¶30). The complaint does not contain a detailed claim chart, but the core infringement theory is that the drug product described in Deva's ANDA will contain the specific crystalline form of lenalidomide claimed in the patents-in-suit.

’800 Patent Infringement Allegations

’217 Patent Infringement Allegations

• Identified Points of Contention:
  • Technical Question: The central dispute will be factual and evidentiary: does the active pharmaceutical ingredient (API) in Deva’s proposed generic product in fact consist of the crystalline hemihydrate form of lenalidomide (Form B) as claimed? This will require detailed analytical testing (e.g., XRPD, DSC) of Deva's ANDA samples.
  • Scope Questions: For the ’217 Patent, assuming the presence of the claimed hemihydrate is established, a further question may arise regarding the scope of "greater than about 80% by weight." The dispute could focus on the precision of the analytical methods used to determine purity and the proper interpretation of the word "about."

V. Key Claim Terms for Construction

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

• Context and Importance: This term defines the specific crystalline structure of the claimed polymorph. Infringement of the ’800 patent will hinge on whether Deva's product meets the structural and compositional definition of a "hemihydrate," which corresponds to Form B in the patent.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: Parties may argue that "hemihydrate" has a plain and ordinary meaning in chemistry—a crystalline solid containing one molecule of water for every two molecules of the compound—and should not be limited beyond that definition.
  • Evidence for a Narrower Interpretation: The specification extensively defines "Form B" as the claimed hemihydrate and provides a detailed set of characterizing data, including specific XRPD peaks, IR and Raman spectra, and thermal analysis results (’800 Patent, col. 6:52–col. 7:31). A party could argue that the term "hemihydrate" in the context of the patent is implicitly limited to a crystalline form exhibiting these specific disclosed properties.

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

• Context and Importance: This phrase sets the purity threshold for infringement. The dispute will concern both the quantitative measurement and the legal scope of "about." Practitioners may focus on this term because small variations in composition or measurement could determine the outcome of infringement.

• Intrinsic Evidence for Interpretation:

  • Evidence for a Broader Interpretation: The use of "about" suggests the patentee did not intend to be limited to a precise 80.0% cutoff, potentially accounting for standard experimental error in quantitative analysis techniques.
  • Evidence for a Narrower Interpretation: The patent specification provides a clear hierarchy of purity, defining "substantially pure" with tiers of greater than 80%, 90%, 95%, and 97% by weight (’217 Patent, col. 4:35-50). A party could argue that this explicit structure suggests "about 80%" should be construed as the lowest claimed tier and not be expanded significantly, as the patentee knew how to claim higher, more precise purities.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement allegation is based on the assertion that, upon FDA approval, Defendant will intentionally encourage acts of direct infringement with knowledge of the patents (Compl. ¶24, ¶33). The contributory infringement allegation asserts Defendant knows its products are especially adapted for an infringing use and have no substantial non-infringing use (Compl. ¶25, ¶34).
• Willful Infringement: The complaint does not use the term "willful infringement" but alleges the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285 (Compl. ¶28, ¶37). The factual basis for this is Defendant's filing of its ANDA with a Paragraph IV certification, which demonstrates knowledge of the patents-in-suit.

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

• A core issue will be one of polymorph identification: What is the precise crystalline structure of the lenalidomide API in Defendant's proposed generic product? The case will likely depend on competing expert analyses and whether the data show Defendant's product meets the definition of the "hemihydrate" (Form B) claimed in the patents.
• A key evidentiary question will be one of quantitative purity: Assuming Defendant's product contains the claimed polymorph, does it meet the "greater than about 80% by weight" purity threshold of the ’217 patent? This will turn on the reliability of the analytical methods used to measure the composition of the solid form.
• A central legal question may be one of claim scope: How should the term "hemihydrate" be construed? Will it be given its plain chemical meaning, or will it be limited to a polymorph exhibiting the specific characterization data for "Form B" disclosed in the patent specification?