DCT

2:19-cv-05804

Celgene Corp v. Breckenridge Pharmaceutical Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:19-cv-05804, D.N.J., 02/14/2019
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendants' systematic and continuous business contacts with the state, including being registered to conduct business and operate as a drug wholesaler in New Jersey.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's POMALYST® drug product constitutes an act of infringement of three patents covering specific crystalline forms of pomalidomide.
  • Technical Context: The technology relates to pharmaceutical polymorphs—distinct crystalline structures of the same active pharmaceutical ingredient—which can exhibit different physical properties critical for drug manufacturing, stability, and bioavailability.
  • Key Procedural History: The litigation was triggered by Defendants' filing of ANDA No. 210111, which seeks FDA approval to market a generic drug prior to the expiration of the patents-in-suit. The complaint notes that Defendants had previously sent Paragraph IV Certification notice letters concerning other, unrelated patents covering pomalidomide.

Case Timeline

Date Event
2017-04-11 ANDA No. 210111 pending before the FDA since at least this date
2017-05-26 Priority Date for U.S. Patent No. 10,093,647
2017-09-22 Priority Date for U.S. Patent Nos. 10,093,648 and 10,093,649
2018-10-09 U.S. Patent Nos. 10,093,647, 10,093,648, and 10,093,649 Issued
2018-11-20 Plaintiff sent letter to Defendants alleging likely infringement of patents-in-suit
2019-02-14 Complaint Filed

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

U.S. Patent No. 10,093,647 - "Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione dihydrate, compositions and methods of use thereof"

The Invention Explained

  • Problem Addressed: The patent's background section explains that a single chemical compound can exist in different solid crystalline forms, known as polymorphs, which can significantly affect a drug's physical and chemical properties, such as stability, solubility, and bioavailability. The discovery of new, useful polymorphs is described as a complex and critical challenge in pharmaceutical development. (’647 Patent, col. 1:21-47).
  • The Patented Solution: The invention is a specific crystalline form of pomalidomide known as a "dihydrate," meaning it incorporates approximately two molecules of water for every molecule of the active ingredient within its crystal structure. This distinct solid form is primarily identified by its unique "fingerprint" as measured by X-ray powder diffraction (XRPD), which produces a characteristic pattern of peaks at specific angles. (’647 Patent, Abstract; col. 4:65-67; FIG. 1). The patent provides a representative XRPD pattern chart displaying the characteristic peaks that define the patented crystalline dihydrate form (’647 Patent, FIG. 1).
  • Technical Importance: Identifying stable and reproducible crystalline forms of an active pharmaceutical ingredient is crucial for ensuring consistent quality, shelf life, and therapeutic performance in a commercial drug product. (’647 Patent, col. 1:36-47).

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the patent; Independent Claim 1 is the broadest composition of matter claim. (Compl. ¶35).
  • Essential elements of Independent Claim 1:
    • A crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione dihydrate,
    • having an X-ray powder diffraction pattern comprising peaks at 13.9, 16.6, and 25.5 degrees 2θ±0.2 degrees 2θ. (’647 Patent, col. 15:35-38).
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,093,648 - "Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione hemihydrate, compositions and methods of use thereof"

The Invention Explained

  • Problem Addressed: Similar to the ’647 Patent, this patent addresses the general problem in pharmaceutical sciences of identifying and characterizing novel crystalline forms of a drug that may offer advantages in manufacturing, formulation, stability, or bioavailability over previously known forms. (’648 Patent, col. 1:21-47).
  • The Patented Solution: The invention provides a different crystalline form of pomalidomide known as a "hemihydrate," a structure that incorporates approximately one molecule of water for every two molecules of the drug. Like the dihydrate form, this polymorph is defined by a unique XRPD pattern that serves as its structural fingerprint. (’648 Patent, Abstract; col. 4:65-67; FIG. 1). The patent provides an XRPD pattern chart that visually represents the unique crystalline structure of the claimed hemihydrate form (’648 Patent, FIG. 1).
  • Technical Importance: The creation of a distinct, stable hydrated form provides an alternative solid-state version of the drug, which may possess unique properties beneficial for developing a safe, effective, and commercially viable pharmaceutical product. (’648 Patent, col. 1:36-47).

Key Claims at a Glance

  • The complaint asserts "one or more claims" of the patent; Independent Claim 1 is the broadest composition of matter claim. (Compl. ¶47).
  • Essential elements of Independent Claim 1:
    • A crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione hemihydrate,
    • having an X-ray powder diffraction pattern comprising peaks at 12.0, 17.2, and 25.6 degrees 2θ±0.2 degrees 2θ. (’648 Patent, col. 15:47-50).
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,093,649 - "Crystalline 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione monohydrate, compositions and methods of use thereof"

Technology Synopsis

  • The patent addresses the need for novel, stable, and useful solid forms of pomalidomide for pharmaceutical use. It discloses and claims a "monohydrate" crystalline form, in which the crystal lattice incorporates approximately one molecule of water for each molecule of pomalidomide. (’649 Patent, Abstract; col. 1:36-47).

Asserted Claims

  • The complaint asserts "one or more claims," with Claim 1 being the broadest independent claim. (Compl. ¶59).

Accused Features

  • The complaint alleges on information and belief that Defendants' ANDA Products contain the crystalline pomalidomide monohydrate as set forth in the claims of the ’649 Patent. (Compl. ¶56).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are "Breckenridge's ANDA Products," which are generic pomalidomide capsules in 1 mg, 2 mg, 3 mg, and 4 mg dosages, for which Defendants seek FDA approval under ANDA No. 210111. (Compl. ¶1).
  • Functionality and Market Context:
    • The products are proposed generic versions of POMALYST®, an FDA-approved medication used for the treatment of multiple myeloma. (Compl. ¶9).
    • The act of infringement alleged is the filing of the ANDA itself, which seeks approval to market these products before the expiration of the patents-in-suit. (Compl. ¶¶35, 47, 59). The technical basis for infringement is the allegation that these generic products contain the specific crystalline forms of pomalidomide claimed in the patents-in-suit. (Compl. ¶¶32, 44, 56).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed claim chart or specific factual allegations mapping elements of the asserted claims to the accused product. The infringement theory is based on the allegation, made "on information and belief," that the active pharmaceutical ingredient in Defendants' ANDA Products is the specific crystalline dihydrate and hemihydrate forms of pomalidomide claimed in the ’647 and ’648 patents, respectively. (Compl. ¶¶32, 44).

  • Identified Points of Contention:
    • Evidentiary Question: The central dispute will be a factual and technical one: Does the pomalidomide in Defendants' ANDA product actually exist in the crystalline dihydrate or hemihydrate forms as claimed? This question will likely be resolved through discovery and competing expert analyses of the accused products using techniques like X-ray powder diffraction.
    • Scope Question: A key legal and technical question will be whether the XRPD pattern of the accused product exhibits peaks at the specific angular locations recited in the claims (e.g., "13.9, 16.6, and 25.5 degrees 2θ±0.2 degrees 2θ" for the ’647 Patent). The analysis will focus on whether the measured peaks from the accused product fall within the claimed ranges, considering the specified margin of error (±0.2 degrees 2θ).

V. Key Claim Terms for Construction

  • The Term: "having an X-ray powder diffraction pattern comprising peaks at [list of] degrees 2θ±0.2 degrees 2θ"
  • Context and Importance: This phrase is the primary technical limitation defining the patented crystalline forms. The infringement analysis will turn almost exclusively on whether the physical structure of Defendants' product meets this definition. Practitioners may focus on this term because the presence and location of these peaks are the dispositive evidence of the claimed polymorph.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of the open-ended term "comprising" suggests that the presence of the recited peaks is sufficient for infringement, even if other, unlisted peaks are also present in the product's diffraction pattern. The patent specification states that the crystalline form is "characterized by XRPD peaks located at" the claimed positions, which may support the view that these are the essential identifiers. (’647 Patent, col. 5:50-54).
    • Evidence for a Narrower Interpretation: The specification provides representative XRPD patterns in figures and detailed peak lists in tables, including data on relative peak intensities. (e.g., ’647 Patent, FIG. 1; Table 1). A party could argue that for a pattern to truly match, it must not only have peaks at the claimed locations but also exhibit a substantially similar overall pattern, including similar relative intensities, as depicted in the patent's examples. A significant deviation in the overall pattern, it might be argued, could indicate a different polymorph, even if some peaks coincidentally overlap.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will induce infringement by encouraging the use of the ANDA products, with knowledge of the patents and that such use constitutes infringement. (Compl. ¶¶38, 50, 62). Contributory infringement is also alleged, based on the assertion that the products are especially adapted for an infringing use and have no substantial non-infringing use. (Compl. ¶¶39, 51, 63).
  • Willful Infringement: The complaint does not contain a formal allegation of willful infringement. It does, however, request a finding that the case is "exceptional" and an award of attorneys' fees under 35 U.S.C. § 285. (Compl. ¶¶42, 54, 66).

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

The resolution of this case will likely depend on the answers to two central questions:

  • A primary issue will be one of empirical evidence: Does the active pharmaceutical ingredient in Defendants' ANDA product, when subjected to X-ray powder diffraction analysis, produce a pattern with peaks located at the specific angular positions required by the asserted claims of the patents-in-suit?
  • A secondary issue may be one of holistic comparison versus literal presence: In determining infringement, will the analysis be confined to literally identifying the claimed peaks in the accused product's XRPD data, or will the court also consider whether the overall "fingerprint" of the accused product's pattern is consistent with the representative examples disclosed in the patents' specifications?