DCT

2:19-cv-14731

Celgene Corp v. Cipla Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:19-cv-14731, D.N.J., 07/03/2019
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey based on Defendant’s systematic and continuous business contacts within the state, including the marketing and sale of pharmaceutical products, and because the district is a likely destination for the accused generic products. The complaint also notes that Defendant has previously been sued in the district and has not challenged personal jurisdiction.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's REVLIMID® (lenalidomide) capsules constitutes infringement of twelve U.S. patents covering specific crystalline forms of lenalidomide, pharmaceutical compositions, and methods for treating multiple myeloma and myelodysplastic syndromes.
  • Technical Context: The dispute centers on the pharmaceutical compound lenalidomide, a significant cancer therapeutic, and specifically its solid-state crystalline forms (polymorphs), which can influence a drug's stability, solubility, and therapeutic performance.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 213165 to the FDA. Defendant provided a Paragraph IV Certification alleging that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic products, and sent a corresponding notice letter to Plaintiff on or after May 30, 2019, triggering this lawsuit.

Case Timeline

Date Event
2002-05-17 Earliest Priority Date for ’569, ’498, ’095, ’621, ’622 Patents
2002-10-15 Earliest Priority Date for ’740, ’717, ’120 Patents
2003-09-04 Earliest Priority Date for ’800, ’217 Patents
2007-03-13 U.S. Patent No. 7,189,740 Issues
2008-12-16 U.S. Patent No. 7,465,800 Issues
2010-12-21 U.S. Patent No. 7,855,217 Issues
2011-06-28 U.S. Patent No. 7,968,569 Issues
2013-03-26 U.S. Patent No. 8,404,717 Issues
2013-09-10 U.S. Patent No. 8,530,498 Issues
2014-02-11 U.S. Patent No. 8,648,095 Issues
2015-06-16 U.S. Patent No. 9,056,120 Issues
2015-08-11 U.S. Patent Nos. 9,101,621 & 9,101,622 Issue
2019-05-30 Earliest date Cipla sent Paragraph IV Notice Letter
2019-07-03 Complaint Filing Date

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 (’800 Patent).

The Invention Explained

  • Problem Addressed: The patent's background section notes that chemical compounds can exist in different solid crystalline forms, or polymorphs, which can have different physical properties such as solubility, stability, and bioavailability (’800 Patent, col. 2:20-34). For a pharmaceutical drug, controlling the polymorphic form is critical for ensuring consistent quality, safety, and efficacy, and can provide significant manufacturing and therapeutic benefits (’800 Patent, col. 2:53-56).
  • The Patented Solution: The patent discloses the discovery and characterization of several new polymorphic forms of the compound lenalidomide, identified as Forms A through H (’800 Patent, col. 3:60-63). The invention provides these specific solid forms, methods of making them, and pharmaceutical compositions containing them, thereby allowing for the creation of a stable and effective drug product (’800 Patent, Abstract). The patent uses analytical techniques to define these forms, such as the X-ray powder diffraction (XRPD) pattern for Form B (the claimed hemihydrate) shown in Figure 6 (Compl., Ex. A, p. 36).
  • Technical Importance: The isolation of stable, well-characterized polymorphs is a critical step in pharmaceutical development, enabling the production of a consistent drug substance with predictable performance for treating diseases like cancer and autoimmune disorders (’800 Patent, col. 2:12-19).

Key Claims at a Glance

  • The complaint does not specify which claims are asserted, alleging infringement of "one or more of the claims" (Compl. ¶30). Independent claim 1 is representative of the patent's core composition claims.
  • Independent Claim 1: A composition of matter comprising:
    • 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 (’217 Patent).

The Invention Explained

  • Problem Addressed: As a divisional of the application leading to the ’800 Patent, this patent addresses the same technical problem: the need for well-defined, stable polymorphic forms of lenalidomide to ensure consistent and effective pharmaceutical products (’217 Patent, col. 2:25-40).
  • The Patented Solution: This patent claims solid forms of lenalidomide that contain the crystalline hemihydrate form (also known as Form B) at specific levels of purity (’217 Patent, col. 1:1-12). By claiming a solid form that is substantially pure hemihydrate, the invention provides a composition with predictable physical and chemical properties essential for pharmaceutical manufacturing and therapeutic use (’217 Patent, Abstract).
  • Technical Importance: Claiming a specific polymorphic form at a defined level of purity provides a basis for a drug product with reliable characteristics, which is a key requirement for regulatory approval and commercial manufacturing of pharmaceuticals (’217 Patent, col. 2:52-57).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more of the claims" (Compl. ¶39). Independent claim 1 is representative.
  • Independent Claim 1: A solid form composition comprising:
    • 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.

Multi-Patent Capsules

  • U.S. Patent Nos. 7,968,569; 8,530,498; 8,648,095; 9,101,621; and 9,101,622:
    • Technology Synopsis: These patents claim methods for treating, preventing, or managing multiple myeloma. The claimed methods involve administering an immunomodulatory compound, specifically lenalidomide, often in specific dosing cycles or in combination with other active agents like dexamethasone or a proteasome inhibitor (Compl. ¶¶6-10).
    • Asserted Claims: One or more claims of each patent (Compl. ¶¶48, 57, 66, 75, 84).
    • Accused Features: Cipla’s Proposed Products are accused of infringing these method patents because they are generic versions of REVLIMID®, which is approved for treating multiple myeloma, and their use will follow the approved labeling instructions (Compl. ¶16).
  • U.S. Patent Nos. 7,189,740; 8,404,717; and 9,056,120:
    • Technology Synopsis: These patents claim methods for treating, preventing, or managing myelodysplastic syndromes (MDS). The methods comprise administering lenalidomide, either alone or as a combination therapy with an agent like azacitidine, according to specified dosing regimens (Compl. ¶¶11-13).
    • Asserted Claims: One or more claims of each patent (Compl. ¶¶93, 102, 111).
    • Accused Features: Cipla’s Proposed Products are accused of infringing because they are generic versions of REVLIMID®, which is also approved for treating MDS, and their use is expected to follow the instructions on the REVLIMID® label (Compl. ¶16).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are "Cipla’s Proposed Products," which are 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg generic lenalidomide capsules for which Cipla seeks FDA approval via ANDA No. 213165 (Compl. ¶25).

Functionality and Market Context

The complaint alleges that these products contain lenalidomide as the active pharmaceutical ingredient and are generic versions of Celgene's REVLIMID® product (Compl. ¶1). As generic equivalents, they are intended to be used for the same medical indications as REVLIMID®, which include the treatment of multiple myeloma and myelodysplastic syndromes (Compl. ¶1, ¶16). The complaint alleges that upon FDA approval, Cipla will manufacture, use, sell, or import these products in the United States (Compl. ¶26).

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim chart analysis. It is a notice pleading filed under the Hatch-Waxman Act, where the statutory act of infringement is the filing of the ANDA itself (Compl. ¶¶30, 39). The complaint’s infringement theory is therefore based on the premise that the product described in Cipla's ANDA, if approved and marketed, would directly infringe the asserted patents.

For the composition-of-matter patents (’800 and ’217), the infringement allegation is based on the assertion that Cipla's Proposed Products will contain the claimed crystalline hemihydrate form of lenalidomide (Compl. ¶14). For the method-of-use patents (e.g., ’569, ’740), the infringement allegation is based on the assertion that the labeling for Cipla’s Proposed Products will instruct and encourage medical professionals and patients to administer the drug according to the claimed methods for treating multiple myeloma and MDS (Compl. ¶16).

  • Identified Points of Contention:
    • Scope Questions: For the composition patents, a central question will be the proper construction of claim terms defining the crystalline structure (e.g., "hemihydrate") and purity ("greater than about 80% by weight"). The scope of these terms, defined by analytical data in the patents, will determine whether Cipla’s product falls within the claims. For the method patents, a key question may be whether the term "treating" requires a specific patient outcome that the ANDA filer’s proposed label does not guarantee.
    • Technical Questions: A primary technical dispute for the ’800 and ’217 Patents will be the actual physical form of the lenalidomide in Cipla's Proposed Products. The case will likely involve competing expert analyses of the data from Cipla's confidential ANDA submission to determine if it meets the claimed XRPD, DSC, and other analytical "fingerprints" of the patented polymorph. For the method patents, a question will be whether the proposed product label encourages, recommends, or promotes an infringing use, or if substantial non-infringing uses exist.

V. Key Claim Terms for Construction

For the ’800 Patent

  • The Term: "crystalline ... hemihydrate" (from claim 1)
  • Context and Importance: This term defines the specific polymorphic form of lenalidomide at issue. The entire infringement analysis for the ’800 Patent hinges on whether Cipla’s product contains this exact crystalline structure. Practitioners may focus on this term because polymorphism is central to pharmaceutical patentability and infringement often turns on subtle differences in crystal structure detectable only by sophisticated analytical techniques.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes the general process for making polymorphs, which could suggest that minor process variations resulting in slight analytical differences are still within the scope of the invention (’800 Patent, col. 5:12-32).
    • Evidence for a Narrower Interpretation: The patent provides highly specific analytical data to define the hemihydrate form (Form B), including characteristic XRPD peaks, IR and Raman spectra, and DSC thermograms (’800 Patent, col. 6:55-68). This detailed "fingerprint" may be used to argue that the claim is limited to a crystalline form that precisely matches this data.

For the ’217 Patent

  • The Term: "present at greater than about 80% by weight of the solid form" (from claim 1)
  • Context and Importance: This term establishes a purity threshold for the claimed composition. The infringement analysis will depend on both the measured purity of Cipla’s product and the legal interpretation of the flexibility afforded by the word "about." Practitioners may focus on this term because disputes over purity levels and the meaning of "about" are common in pharmaceutical patent cases.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification discloses progressively purer embodiments, claiming compositions that are "greater than about 80%," "greater than about 90%," and "greater than about 95%" pure, suggesting that "about 80%" is the start of a range and not a rigid floor (’217 Patent, col. 4:38-44).
    • Evidence for a Narrower Interpretation: A party seeking a narrower construction might argue that the term "about" should be limited by the precision of the analytical methods described in the specification for determining polymorphic purity (’217 Patent, col. 16:3-16).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for each asserted patent. The basis for inducement is the allegation that Cipla’s product labeling and instructions will actively encourage physicians and patients to use the generic drug in a manner that infringes the method-of-use claims (Compl. ¶¶33, 42). The basis for contributory infringement is the allegation that Cipla's product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶¶34, 43).
  • Willful Infringement: The complaint does not explicitly allege willful infringement. However, for each asserted patent, it alleges that the case is "an exceptional one" and seeks an award of reasonable attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶37, 46).

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

  • A core issue will be one of physical identity: Does the lenalidomide active ingredient in Cipla’s ANDA product possess the specific crystalline structure and purity of the "hemihydrate" form as defined by the claims and analytical data of the ’800 and ’217 patents, or is it a different, non-infringing polymorph?
  • A key question for the method-of-use patents will be inevitable infringement: Will the proposed labeling for Cipla’s generic product necessarily lead medical professionals to prescribe it according to the specific dosing regimens for multiple myeloma and MDS claimed in Celgene's method patents?
  • Underlying the entire case is the question of patent validity: As is standard in ANDA litigation, a central part of the dispute will be whether Cipla can prove by clear and convincing evidence that Celgene's asserted patent claims are invalid (e.g., for obviousness or lack of written description), as it certified to the FDA.