DCT

2:17-cv-02528

Celgene Corp v. Zydus Pharma USA Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:17-cv-02528, D.N.J., 04/12/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant Zydus USA Inc. having its principal place of business in the district, maintaining systematic and continuous contacts with the state, and the district being a likely destination for the accused generic drug product.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) with the U.S. Food and Drug Administration to market generic versions of Celgene's cancer drug REVLIMID® (lenalidomide) constitutes an act of infringement of seven U.S. patents.
  • Technical Context: The dispute is in the pharmaceutical sector and concerns patents covering specific crystalline forms (polymorphs) of the active pharmaceutical ingredient lenalidomide, as well as methods of using it to treat multiple myeloma.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants’ submission of ANDA No. 210154 and a subsequent Paragraph IV Certification notice letter sent to Celgene, alleging that the patents-in-suit are invalid, unenforceable, or will not be infringed. The complaint notes a related case involving the same patents against a different generic manufacturer, Celgene Corp. v. Dr. Reddy's Laboratories, Ltd.

Case Timeline

Date Event
2002-05-17 Earliest Priority Date for ’569, ’498, ’095, ’621, ’622 Patents
2003-09-04 Earliest Priority Date for ’800 and ’217 Patents
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
2013-09-10 U.S. Patent No. 8,530,498 Issues
2014-02-11 U.S. Patent No. 8,648,095 Issues
2015-08-11 U.S. Patent No. 9,101,621 Issues
2015-08-11 U.S. Patent No. 9,101,622 Issues
2017-02-27 Earliest Date Zydus Sent Paragraph IV Notice Letter to Celgene
2017-04-12 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 (Compl. ¶7).

The Invention Explained

  • Problem Addressed: The patent’s background section explains that many chemical compounds can exist in different solid crystal forms, or "polymorphs," which can exhibit different physical and chemical properties such as solubility, stability, and bioavailability (’800 Patent, col. 2:20-33). For a pharmaceutical drug, identifying and controlling the specific polymorphic form is critical for manufacturing consistency, product stability, and regulatory approval (’800 Patent, col. 2:33-43).
  • The Patented Solution: The invention discloses and characterizes several new polymorphic forms of the compound lenalidomide, designated as Forms A, B, C, D, E, F, G, and H (’800 Patent, col. 2:58-62). The patent provides detailed analytical data, including X-ray powder diffraction (XRPD) patterns and thermogravimetric analysis (TGA) curves, to define these distinct crystalline structures, thereby providing a basis for producing a consistent and stable drug product (’800 Patent, col. 2:50-55; FIG. 6).
  • Technical Importance: The discovery and characterization of stable, manufacturable polymorphs of an active pharmaceutical ingredient is a critical step in drug development, enabling consistent formulation and therapeutic performance.

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’800 patent (Compl. ¶36). Independent claim 1 is asserted.
  • 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 (Compl. ¶8).

The Invention Explained

  • Problem Addressed: As with the parent ’800 Patent, this invention addresses the technical challenge of ensuring pharmaceutical compositions contain a consistent, stable, and pure crystalline form of a drug, which is essential for predictable performance and regulatory compliance (’217 Patent, col. 2:23-48).
  • The Patented Solution: The invention claims solid forms of lenalidomide that are "substantially pure" of a specific polymorph, the hemihydrate form (referred to as Form B in the specification) (’217 Patent, col. 4:32-49). By claiming compositions with defined purity levels (e.g., greater than 80% by weight of the hemihydrate form), the invention provides a standard for a consistent drug substance (’217 Patent, col. 22:30-33).
  • Technical Importance: Claiming a specific level of polymorphic purity is a key strategy for protecting a drug product, as it sets a clear and quantifiable standard that a generic competitor must either meet (and infringe) or design around.

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims of the ’217 patent (Compl. ¶45). Independent claims 1, 2, 3, and 4 are asserted.
  • 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.
  • Independent claims 2, 3, and 4 are substantially similar, claiming purity levels greater than about 90%, 95%, and 97%, respectively.

U.S. Patent No. 7,968,569 - “Methods For Treatment of Multiple Myeloma Using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione”

  • Patent Identification: U.S. Patent No. 7,968,569, “Methods For Treatment of Multiple Myeloma Using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione,” issued June 28, 2011 (Compl. ¶9).
  • Technology Synopsis: The patent claims methods of treating multiple myeloma by administering a specific cyclical dosing regimen of lenalidomide, optionally in combination with dexamethasone.
  • Asserted Claims: The complaint alleges infringement of "one or more" of the patent's claims (Compl. ¶54).
  • Accused Features: Defendants are accused of infringement by seeking FDA approval to market a generic lenalidomide product with labeling that will instruct users to follow the patented treatment methods (Compl. ¶16, 57).

U.S. Patent No. 8,530,498 - “Methods For Treating Multiple Myeloma With 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl) piperidine-2,6-dione”

  • Patent Identification: U.S. Patent No. 8,530,498, “Methods For Treating Multiple Myeloma With 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl) piperidine-2,6-dione,” issued September 10, 2013 (Compl. ¶10).
  • Technology Synopsis: The patent claims methods of treating various subtypes of multiple myeloma by administering lenalidomide according to a specified daily dosing schedule.
  • Asserted Claims: The complaint alleges infringement of "one or more" of the patent's claims (Compl. ¶63).
  • Accused Features: The accused instrumentality is the proposed generic product, which will allegedly be prescribed and used according to the patented methods based on its FDA-approved labeling (Compl. ¶16, 66).

U.S. Patent No. 8,648,095 - “Methods For Treating Multiple Myeloma Using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione In Combination With Proteasome Inhibitor”

  • Patent Identification: U.S. Patent No. 8,648,095, “Methods For Treating Multiple Myeloma Using 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione In Combination With Proteasome Inhibitor,” issued February 11, 2014 (Compl. ¶11).
  • Technology Synopsis: The patent claims a method of treating multiple myeloma that comprises administering lenalidomide in combination with a second active agent, a proteasome inhibitor.
  • Asserted Claims: The complaint alleges infringement of "one or more" of the patent's claims (Compl. ¶72).
  • Accused Features: Infringement is alleged based on the future, intended use of the generic product in combination therapies, as allegedly will be encouraged by the product's labeling (Compl. ¶16, 75).

U.S. Patent No. 9,101,621 - “Methods For Treating Multiple Myeloma With 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione After Stem Cell Transplantation”

  • Patent Identification: U.S. Patent No. 9,101,621, “Methods For Treating Multiple Myeloma With 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione After Stem Cell Transplantation,” issued August 11, 2015 (Compl. ¶12).
  • Technology Synopsis: The patent claims methods of treating multiple myeloma in a specific patient population—those who have previously received a stem cell transplant—by administering lenalidomide.
  • Asserted Claims: The complaint alleges infringement of "one or more" of the patent's claims (Compl. ¶81).
  • Accused Features: The accused act is the filing of an ANDA for a product that will allegedly be prescribed for the patented method of use, thereby inducing infringement (Compl. ¶16, 84).

U.S. Patent No. 9,101,622 - “Methods For Treating Newly-Diagnosed Multiple Myeloma 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione In Combination With Dexamethasone”

  • Patent Identification: U.S. Patent No. 9,101,622, “Methods For Treating Newly-Diagnosed Multiple Myeloma 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione In Combination With Dexamethasone,” issued August 11, 2015 (Compl. ¶13).
  • Technology Synopsis: The patent claims methods of treating a specific patient population—those newly diagnosed with multiple myeloma—using a combination of lenalidomide and dexamethasone.
  • Asserted Claims: The complaint alleges infringement of "one or more" of the patent's claims (Compl. ¶90).
  • Accused Features: Defendants are accused of infringement by seeking FDA approval for a product whose label will allegedly encourage its use in the patented combination therapy method (Compl. ¶16, 93).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are "Zydus's Proposed Products," identified as lenalidomide capsules in 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg strengths (Compl. ¶31). The act of infringement giving rise to the suit is Zydus's filing of Abbreviated New Drug Application (ANDA) No. 210154 with the FDA (Compl. ¶1).

Functionality and Market Context

  • The complaint alleges that the Proposed Products are generic versions of Celgene's REVLIMID®, an FDA-approved medication for treating certain forms of cancer, including multiple myeloma (Compl. ¶1, 14). The technical functionality of the Proposed Products is therefore alleged to be identical to REVLIMID®, delivering the active ingredient lenalidomide for therapeutic effect (Compl. ¶14).
  • The complaint frames the dispute in the context of Zydus seeking to enter the U.S. market with a generic version of a branded drug prior to the expiration of the patents listed in the FDA's Orange Book for that drug (Compl. ¶1, 15).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim chart analysis. The central allegation is that Zydus’s submission of its ANDA constitutes a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), because the product that will be commercially manufactured and sold upon FDA approval will infringe the patents-in-suit (Compl. ¶36, 45, 54, 63, 72, 81, 90). For the composition patents (’800 and ’217), the infringement theory rests on the assertion that the proposed generic product is or contains the claimed crystalline form of lenalidomide (Compl. ¶14). For the method of use patents (’569, ’498, ’095, ’621, and ’622), the infringement theory is based on inducement, alleging that the labeling for the proposed generic product will instruct and encourage medical professionals to administer it according to the patented methods (Compl. ¶16).

  • Identified Points of Contention:
    • Scope Questions: A primary question for the composition claims will be the scope of the term "hemihydrate" (’800 Patent) and the purity thresholds (e.g., "greater than about 80% by weight") for the claimed solid form (’217 Patent). The litigation may focus on whether the analytical data for Zydus's proposed product falls within the boundaries of these claim terms.
    • Technical Questions: A central factual dispute for the composition patents will be the actual polymorphic form and purity of the lenalidomide in Zydus's ANDA product. For the method patents, a key question will be whether the language in Zydus's proposed label meets the legal standard for encouraging, recommending, or promoting an infringing use by physicians or patients.

V. Key Claim Terms for Construction

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

  • Context and Importance: This term defines the specific crystalline structure of the claimed compound. Infringement of the ’800 Patent will depend on whether Zydus's proposed product contains lenalidomide in this specific crystal lattice form, which incorporates approximately one molecule of water for every two molecules of lenalidomide. Practitioners may focus on this term because polymorphic identity is the dispositive issue for infringement of a composition-of-matter patent in a pharmaceutical case.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The plain meaning of "hemihydrate" is a well-understood chemical term of art, which may suggest a broader construction not limited to the specific examples in the patent.
    • Evidence for a Narrower Interpretation: The specification explicitly identifies "Form B" as a hemihydrate and provides extensive characterization data, stating that calculations from TGA data "indicate that Form B is a hemihydrate" and that it "typically loses about 3.1% volatiles up to about 175° C." (’800 Patent, col. 7:1-6). Parties may argue that the term "hemihydrate" as used in the claim should be construed as being limited to a crystalline form exhibiting the specific XRPD, TGA, and DSC characteristics disclosed for Form B in the patent's figures and detailed description (’800 Patent, FIG. 6, 9).

  • The Term: "A solid form ... comprising crystalline ... hemihydrate ... present at greater than about 80% by weight of the solid form" (from ’217 Patent, Claim 1)

  • Context and Importance: This phrase sets the purity threshold for the claimed crystalline form. The dispute will likely involve not only the identity of the polymorph in the accused product but also its concentration relative to any other forms (crystalline or amorphous). The construction of "about" will be critical in determining the scope of the purity requirement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The use of the word "about" explicitly contemplates that the composition does not have to be strictly and exactly "greater than 80%." This could support a construction that includes compositions slightly below the 80% threshold.
    • Evidence for a Narrower Interpretation: The specification provides a clear hierarchy of purity, describing compositions that are "more preferably greater than about 90%," "even more preferably greater than about 95%," and "most preferably greater than about 97%" (’217 Patent, col. 4:41-49). This detailed description of increasing purity levels may be used to argue that "about 80%" should be interpreted narrowly and precisely, as the patentee clearly contemplated and claimed higher, distinct thresholds.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Zydus will induce infringement of all asserted patents by encouraging acts of direct infringement and will contributorily infringe because its proposed products are especially adapted for an infringing use with no substantial non-infringing use (Compl. ¶39-40, 48-49, 57-58, 66-67, 75-76, 84-85, 93-94). The basis for inducement of the method claims is the allegation that Zydus's product labeling will instruct physicians and patients to use the drug in an infringing manner (Compl. ¶16).
  • Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, for each patent, it alleges the case is "an exceptional one" and requests an award of reasonable attorneys' fees under 35 U.S.C. § 285 (Compl. ¶43, 52, 61, 70, 79, 88, 97). The factual basis for this allegation is not detailed beyond Zydus's filing of the ANDA with a Paragraph IV certification.

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

  • A central evidentiary question will be one of polymorphic identity and purity: What are the actual physical and chemical characteristics of the lenalidomide active ingredient in Zydus's proposed generic product? Discovery and expert analysis will focus on whether Zydus's product contains the "hemihydrate" form claimed by the ’800 Patent and whether it meets the "substantially pure" thresholds claimed by the ’217 Patent.
  • A key legal and factual issue for the five method-of-use patents will be induced infringement: Assuming the asserted claims are valid, does the proposed product labeling that Zydus submitted to the FDA contain language that actively encourages or instructs medical professionals to prescribe the generic drug in a manner that practices the specific dosing, patient population, and combination therapy steps required by the claims?
  • A foundational issue for the entire case will be validity: Zydus's Paragraph IV notice asserts that the patents are invalid. The litigation will therefore focus heavily on Zydus's attempts to prove, by clear and convincing evidence, that the asserted claims are anticipated by or would have been obvious in light of prior art existing before Celgene's inventions.