DCT

2:17-cv-06163

Celgene Corp v. Cipla Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:17-cv-06163, D.N.J., 08/15/2017
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on Defendant's systematic and continuous business contacts with the state, including the marketing and sale of pharmaceutical products.
  • Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) seeking approval to market generic lenalidomide capsules infringes seven patents covering specific crystalline forms of lenalidomide and methods of using it to treat multiple myeloma.
  • Technical Context: The dispute centers on lenalidomide (marketed as REVLIMID®), a significant immunomodulatory drug used primarily to treat blood cancers, and the specific physical forms (polymorphs) and treatment protocols that enable its safe and effective use.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Defendant’s submission of an ANDA with a Paragraph IV certification to the FDA. Defendant's certification alleges that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by its proposed generic products.

Case Timeline

Date Event
2002-05-17 Earliest Priority Date for ’569, ’498, ’095, ’621, and ’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
2017-06-30 Earliest date Cipla sent Paragraph IV Notice Letter to Celgene
2017-08-15 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,” issued December 16, 2008 (’800 Patent)

The Invention Explained

  • Problem Addressed: The patent’s background section explains that a single chemical compound can exist in different solid crystalline forms, or polymorphs, which can have different physical and chemical properties such as solubility, stability, and bioavailability (’800 Patent, col. 2:20-33). For a pharmaceutical drug, controlling the polymorphic form is critical for ensuring consistent manufacturing, stability, and therapeutic efficacy, as well as for meeting regulatory standards (’800 Patent, col. 2:33-57).
  • The Patented Solution: The patent discloses the discovery and characterization of several distinct polymorphic forms of the compound lenalidomide, designated as Forms A through H (’800 Patent, col. 2:58-62). The invention provides methods for preparing these specific forms and characterizes them using analytical techniques such as X-ray powder diffraction (XRPD), which produces a unique fingerprint for each crystal structure (see, e.g., ’800 Patent, Fig. 6). This allows for the reliable production of a consistent, stable solid form of the drug for use in pharmaceutical compositions (’800 Patent, Abstract).
  • Technical Importance: Identifying and claiming distinct, stable polymorphs of an active pharmaceutical ingredient is a crucial step in drug development, enabling consistent large-scale manufacturing and predictable performance in a final drug product.

Key Claims at a Glance

  • The complaint asserts "one or more" claims without specification; independent claim 1 is representative (Compl. ¶27).
  • Independent Claim 1 requires:
    • Crystalline 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione
    • hemihydrate
  • The complaint reserves the right to assert other claims, including dependent claims.

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 with the parent ’800 Patent, this invention addresses the need for well-characterized and pure polymorphic forms of lenalidomide to ensure the safety, stability, and efficacy of drug products containing it (’217 Patent, col. 2:41-47).
  • The Patented Solution: The patent claims solid forms of lenalidomide that are "substantially pure," meaning they consist primarily of one specific polymorph and are substantially free of others (’217 Patent, col. 4:32-36). The invention specifies compositions containing a particular crystalline form (the hemihydrate, also known as Form B) at purity levels of greater than 80%, 90%, 95%, or 97% by weight (’217 Patent, col. 4:37-44). This ensures that the final drug product has consistent and predictable physical properties.
  • Technical Importance: Claiming compositions with high polymorphic purity provides a greater degree of control over the final drug product's performance characteristics, which is highly valued in pharmaceutical manufacturing and for regulatory purposes.

Key Claims at a Glance

  • The complaint asserts "one or more" claims without specification; independent claim 1 is representative (Compl. ¶36).
  • Independent Claim 1 requires:
    • 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
  • The complaint reserves the right to assert other claims, including dependent claims.

U.S. Patent No. 7,968,569 (’569 Patent) - “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

  • Technology Synopsis: This patent claims methods of treating multiple myeloma by administering lenalidomide. It specifies particular dosing schedules, such as administering the compound for 21 consecutive days followed by a seven-day rest period, in combination with dexamethasone (’569 Patent, col. 39:11-40:20).
  • Asserted Claims: Independent claims 1, 3, and 13 (Compl. ¶45).
  • Accused Features: Cipla’s proposed generic lenalidomide products are accused of infringing because their intended use, as would be directed by the product label, would fall within the patented methods of treatment (Compl. ¶13, 48).

U.S. Patent No. 8,530,498 (’498 Patent) - “Methods For Treating Multiple Myeloma With 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl) piperidine-2,6-dione,” issued September 10, 2013

  • Technology Synopsis: This patent, a continuation of the application leading to the ’569 patent, also claims methods of treating multiple myeloma. It covers a specific dosing regimen where about 25 mg per day of lenalidomide is administered on a 28-day cycle, which includes a rest period, in combination with dexamethasone (’498 Patent, col. 37:50-38:20).
  • Asserted Claims: Independent claim 1 (Compl. ¶54).
  • Accused Features: Cipla’s proposed product label is expected to instruct physicians and patients to use the generic drug in a way that infringes the claimed treatment method (Compl. ¶13, 57).

U.S. Patent No. 8,648,095 (’095 Patent) - “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

  • Technology Synopsis: This patent covers methods of treating multiple myeloma by administering lenalidomide in combination with a second active agent, which is specified as a proteasome inhibitor (e.g., bortezomib) (’095 Patent, Abstract; col. 39:46-40:9).
  • Asserted Claims: Independent claim 1 (Compl. ¶63).
  • Accused Features: The intended use of Cipla's generic lenalidomide, particularly in combination therapies common for multiple myeloma, is alleged to infringe the patented method (Compl. ¶13, 66).

U.S. Patent No. 9,101,621 (’621 Patent) - “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

  • Technology Synopsis: This patent claims methods of treating multiple myeloma in a specific patient population: those who have previously received a stem cell transplant. The claims cover administering lenalidomide to such patients according to a defined cyclic schedule (’621 Patent, col. 39:15-26).
  • Asserted Claims: Independent claim 1 (Compl. ¶72).
  • Accused Features: Cipla’s proposed generic product is accused of infringing because it will be administered to patients who have had stem cell transplants, thereby practicing the claimed method (Compl. ¶13, 75).

U.S. Patent No. 9,101,622 (’622 Patent) - “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

  • Technology Synopsis: This patent is directed to methods of treating a specific patient population: those newly diagnosed with multiple myeloma. The claimed method involves administering lenalidomide on a 28-day cycle in combination with dexamethasone (’622 Patent, col. 39:25-46).
  • Asserted Claims: Independent claim 1 (Compl. ¶81).
  • Accused Features: The proposed label for Cipla's generic product is expected to instruct its use as a first-line therapy for newly diagnosed patients, which is alleged to infringe the claimed method (Compl. ¶13, 84).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Cipla’s proposed 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg lenalidomide capsules ("Cipla's Proposed Products") for which Defendant filed ANDA No. 210435 with the FDA (Compl. ¶1, 22).
  • Functionality and Market Context: The complaint alleges that Cipla’s Proposed Products are generic versions of Celgene’s REVLIMID® drug product (Compl. ¶1). As such, they are pharmaceutical compositions containing the active ingredient lenalidomide, intended for oral administration. The complaint asserts that the claims of the patents-in-suit cover solid forms of lenalidomide, pharmaceutical compositions containing it, and methods of its use and administration (Compl. ¶11). Cipla is seeking FDA approval to commercially manufacture and sell these generic products in the United States prior to the expiration of the patents-in-suit (Compl. ¶22).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not provide a claim-by-claim infringement analysis or include claim charts. Instead, it alleges infringement based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2)(A), which creates a statutory act of infringement for purposes of establishing jurisdiction in a Hatch-Waxman case (Compl. ¶27, 36, 45, 54, 63, 72, 81). The complaint further alleges that upon FDA approval, Cipla will directly infringe, induce infringement, and contributorily infringe the patents-in-suit by making, using, and selling its Proposed Products (Compl. ¶29-31).

For the composition patents (’800 and ’217), the infringement theory is that Cipla’s Proposed Products will contain the specific crystalline hemihydrate form of lenalidomide, at the claimed purity levels, as required by the claims. For the method of use patents (’569, ’498, ’095, ’621, and ’622), the theory of infringement is that Cipla’s proposed product labeling will instruct physicians and patients to administer the generic drug in a manner that directly infringes the steps of the asserted method claims, which would make Cipla liable for induced infringement (Compl. ¶13, 30, 39).

  • Identified Points of Contention:
    • Technical Questions: For the ’800 and ’217 Patents, a central dispute will likely be the physical characterization of Cipla's product. The key question is whether analytical testing (e.g., XRPD, DSC) of Cipla’s lenalidomide active pharmaceutical ingredient shows that it is the specific "hemihydrate" form claimed in the ’800 Patent and that it meets the polymorphic purity thresholds (e.g., "greater than about 80% by weight") claimed in the ’217 Patent.
    • Scope Questions: For the method patents, a primary question will be whether the language in Cipla’s proposed product label will instruct or encourage medical professionals to prescribe and patients to use the generic drug in a way that meets every limitation of the asserted method claims, including the specified patient populations (e.g., "newly-diagnosed," "after stem cell transplantation"), dosages, and administration schedules.

V. Key Claim Terms for Construction

’800 Patent

  • The Term: "hemihydrate"
  • Context and Importance: This term defines the specific crystalline form of lenalidomide claimed in the ’800 Patent. The infringement analysis for this patent will depend entirely on whether Cipla’s product is properly characterized as a "hemihydrate." Practitioners may focus on this term because its definition is tied to specific, measurable physical properties.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term itself is a standard chemical term referring to a crystalline solid containing one molecule of water for every two molecules of the compound. A party could argue it should be given its plain and ordinary meaning in the field of chemistry.
    • Evidence for a Narrower Interpretation: The specification explicitly links the term "hemihydrate" to the polymorph designated "Form B" (’800 Patent, col. 5:40-41). The patent provides detailed characterization data for Form B, including a statement that it "loses about 3.1% volatiles up to about 175° C. (per approximately 0.46 moles of water)" and has a specific XRPD pattern (’800 Patent, col. 7:1-6; Fig. 6). A party could argue that this detailed description defines and limits the scope of "hemihydrate" to material exhibiting these specific properties.

’217 Patent

  • The Term: "greater than about 80% by weight"
  • Context and Importance: This phrase defines the minimum level of polymorphic purity required by claim 1 of the ’217 Patent. The dispute will likely center on both the measured purity of Cipla's product and the degree of variance permitted by the word "about."
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of "about" explicitly signals that the 80% figure is not a rigid cutoff. The specification discloses a hierarchy of preferred purities, including "more preferably greater than about 90%," "even more preferably greater than about 95%," and "most preferably greater than about 97%" (’217 Patent, col. 4:39-44). This may suggest that "about 80%" was intended to be the start of a broader range of high-purity compositions.
    • Evidence for a Narrower Interpretation: A party could argue that the scope of "about" should be limited by the precision of the analytical techniques (e.g., XRPD) used to measure polymorphic purity, as described in the patent. The explicit listing of progressively higher preferred percentages could also be used to argue that "about 80%" was intended to mean a value close to 80% and not, for example, 75%.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all seven patents-in-suit (e.g., Compl. ¶30, 31, 39, 40). For the method of use patents, induced infringement is a central allegation, based on the assertion that Cipla’s product labeling will instruct users to perform the claimed therapeutic methods (Compl. ¶13). For the composition patents, contributory infringement is alleged on the basis that Cipla’s products are especially adapted for an infringing use and have no substantial non-infringing use (Compl. ¶31).
  • Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, it alleges that Cipla has had knowledge of the patents since at least the time it sent its Paragraph IV Notice Letter (Compl. ¶25, 30). This allegation of pre-suit knowledge could be used to support a later claim for willful infringement based on post-filing conduct. The complaint also requests attorneys' fees under 35 U.S.C. § 285, alleging this is an "exceptional one" (Compl. ¶34), a finding often associated with willfulness or other litigation misconduct.

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

  • A core issue will be one of technical characterization and scope: Does the active ingredient in Cipla’s proposed generic product meet the specific structural and purity requirements of the asserted composition claims? This will likely turn on a battle of experts analyzing whether Cipla's product is the claimed "hemihydrate" form of lenalidomide and whether it is present in a concentration "greater than about 80% by weight."
  • A second central question will be one of inducement and label construction: For the five method of use patents, the case will depend on whether the final, FDA-approved label for Cipla's generic product will be construed as actively instructing or encouraging physicians to prescribe the drug for the specific patient populations (e.g., "newly-diagnosed," "after stem cell transplantation") and according to the claimed dosing schedules.
  • A third fundamental issue, raised by Cipla's Paragraph IV certification, will be patent validity: The court will need to adjudicate Cipla’s assertions that Celgene's patents are invalid, likely focusing on questions of whether the claimed crystalline forms and treatment methods were obvious or anticipated by the prior art at the time of invention.