DCT

2:17-cv-06842

Celgene Corp v. Lotus Pharmaceutical Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:17-cv-06842, D.N.J., 09/06/2017
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant Alvogen maintains its principal place of business in the district, and Defendant Lotus purposefully avails itself of the privilege of doing business in New Jersey through its partner and agent, Alvogen.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's REVLIMID® (lenalidomide) drug products constitutes an act of infringement of sixteen U.S. patents.
  • Technical Context: The patents-in-suit relate to the chemical compound lenalidomide, specific crystalline forms of the compound, methods of its use for treating various cancers, and computer-implemented systems for its safe distribution.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of a Paragraph IV Certification to the FDA, which alleged that Plaintiff's patents are invalid, unenforceable, and/or will not be infringed by the proposed generic products. The complaint notes that other litigations are pending against different generic manufacturers involving some of the same patents, indicating a broad enforcement strategy by Plaintiff to protect its REVLIMID® franchise. Subsequent to the issuance of U.S. Patent No. 6,315,720, an inter partes review resulted in the cancellation of claims 1-9 and 11-32, leaving only claim 10 patentable; this will significantly narrow the scope of litigation concerning that patent.

Case Timeline

Date Event
1996-07-24 U.S. Patent 5,635,517 Priority Date
1997-06-03 U.S. Patent 5,635,517 Issued
2000-10-23 U.S. Patent 6,315,720 Priority Date
2001-11-13 U.S. Patent 6,315,720 Issued
2003-05-13 U.S. Patent 6,561,977 Issued
2004-06-29 U.S. Patent 6,755,784 Issued
2007-03-13 U.S. Patent 7,189,740 Issued
2008-12-16 U.S. Patent 7,465,800 Issued
2010-12-21 U.S. Patent 7,855,217 Issued
2011-06-28 U.S. Patent 7,968,569 Issued
2012-11-20 U.S. Patent 8,315,886 Issued
2013-03-26 U.S. Patent 8,404,717 Issued
2013-09-10 U.S. Patent 8,530,498 Issued
2013-12-01 Alvogen Group, Inc. allegedly became majority shareholder of Lotus
2014-01-07 U.S. Patent 8,626,531 Issued
2014-02-11 U.S. Patent 8,648,095 Issued
2015-06-16 U.S. Patent 9,056,120 Issued
2015-08-11 U.S. Patent 9,101,621 Issued
2015-08-11 U.S. Patent 9,101,622 Issued
2017-07-24 Earliest date Defendants sent Paragraph IV Certification Notice Letter
2017-09-06 Complaint Filing Date

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

U.S. Patent No. 5,635,517 - “Methods of Reducing TNFa Levels with Amino Substituted 2-(2,6-dioxopiperidin-3-yl)-1-oxo-and 1,3-dioxoisoindolines”

The Invention Explained

  • Problem Addressed: The patent’s background section describes that excessive or unregulated production of Tumor Necrosis Factor α (TNFα), a cytokine, has been implicated in a number of disease conditions, including inflammatory diseases like arthritis, cachexia, and the replication of retroviruses such as HIV (’517 Patent, col. 1:12-31).
  • The Patented Solution: The invention provides a method for reducing undesirable levels of TNFα in a mammal by administering a class of non-polypeptide compounds identified as amino-substituted isoindolines (’517 Patent, Abstract; col. 3:15-24). This offers a small-molecule therapeutic approach to modulating the effects of this cytokine.
  • Technical Importance: This approach provided an alternative to prior efforts to suppress TNFα that relied on steroids or antibodies, introducing a class of orally available small molecules for treating cytokine-mediated diseases (’517 Patent, col. 4:5-10).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the patent without specifying which claims will be asserted (Compl. ¶44). The patent contains one independent claim.
  • Independent Claim 1 requires:
    • A method of reducing undesirable levels of TNFα in a mammal
    • Which comprises administering an effective amount of a compound of a specified chemical formula (Formula I).

U.S. Patent No. 6,315,720 - “Methods for delivering a drug to a patient while avoiding the occurrence of an adverse side effect known or suspected of being caused by the drug”

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of distributing potentially hazardous drugs, such as the teratogen thalidomide, to patients who need them while preventing exposure to contraindicated individuals, particularly pregnant women (’720 Patent, col. 1:10-18, col. 2:5-12). It notes the limitations of existing voluntary, survey-based programs in ensuring compliance and limiting distribution to approved participants (’720 Patent, col. 2:14-35).
  • The Patented Solution: The invention is a computer-implemented method that controls drug distribution by requiring the prescriber, pharmacy, and patient to be registered and approved in a central computer-readable storage medium before a prescription can be filled (’720 Patent, Abstract). A key feature is the assignment of patients to different "risk groups" based on predefined parameters, allowing safety requirements to be tailored to the individual's specific level of risk (’720 Patent, col. 2:60-65, col. 6:45-54).
  • Technical Importance: This patent describes a foundational framework for what are now known as Risk Evaluation and Mitigation Strategies (REMS), which are required by the FDA for drugs with known serious safety concerns and have become essential for the marketing of such products.

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specifying which will be asserted (Compl. ¶53). The attached inter partes review certificate indicates that claims 1-9 and 11-32 have been cancelled, leaving Claim 10 as the only remaining patentable claim (’720 Patent, p. 13).
  • Independent Claim 1, now cancelled, required defining patient risk groups, obtaining risk-probative information, and assigning the patient to a risk group within the computer medium.
  • The complaint explicitly reserves the right to assert dependent claims (Compl. ¶¶1, 44, 53).

Multi-Patent Capsule: U.S. Patent Nos. 6,561,977; 6,755,784; 8,315,886; 8,626,531

  • Patent Identification: A family of patents related to the ’720 Patent, all titled "Methods for delivering a drug to a patient while restricting access to the drug by patients for whom the drug may be contraindicated" or similar. Issue dates range from May 13, 2003 to January 7, 2014 (Compl. ¶¶10, 11, 16, 19).
  • Technology Synopsis: These patents claim further refinements and specific implementations of the computer-based controlled drug distribution system described in the ’720 Patent. They add further steps and conditions to the process of authorizing and dispensing prescriptions for high-risk drugs to ensure patient safety and program compliance.
  • Asserted Claims: One or more claims of each patent (Compl. ¶¶62, 71, 116, 143).
  • Accused Features: Defendants' filing of an ANDA for generic lenalidomide, which Plaintiff alleges will require Defendants to implement an infringing drug distribution system to gain FDA approval (Compl. ¶¶62, 71, 116, 143).

Multi-Patent Capsule: U.S. Patent Nos. 7,465,800; 7,855,217

  • Patent Identification: Patents titled "Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione." Issue dates are December 16, 2008 and December 21, 2010 (Compl. ¶¶13, 14).
  • Technology Synopsis: These patents claim specific crystalline forms (polymorphs) of the lenalidomide active pharmaceutical ingredient. Different polymorphic forms of a drug can have different physical properties, such as stability and dissolution rate, which can be critical for formulation and bioavailability.
  • Asserted Claims: One or more claims of each patent (Compl. ¶¶89, 98).
  • Accused Features: The solid form of the lenalidomide active pharmaceutical ingredient contained within Defendants' proposed generic capsules (Compl. ¶¶89, 98).

Multi-Patent Capsule: U.S. Patent Nos. 7,189,740; 7,968,569; 8,404,717; 8,530,498; 8,648,095; 9,056,120; 9,101,621; 9,101,622

  • Patent Identification: A portfolio of patents claiming methods of using lenalidomide to treat specific diseases. Titles include "Methods of Using...for the Treatment and Management of Myelodysplastic Syndromes" and "Methods For Treatment of Multiple Myeloma..." Issue dates range from March 13, 2007 to August 11, 2015 (Compl. ¶¶12, 15, 17, 18, 20, 21, 22, 23).
  • Technology Synopsis: These patents claim methods of treating specific medical conditions, such as Myelodysplastic Syndromes (MDS) and Multiple Myeloma (MM), by administering lenalidomide. Some patents claim use of lenalidomide in combination with other therapeutic agents like dexamethasone or azacitidine.
  • Asserted Claims: One or more claims of each patent (Compl. ¶¶80, 107, 125, 134, 152, 161, 170, 179).
  • Accused Features: The proposed use of Defendants' generic lenalidomide products for the treatment of the claimed indications, which Plaintiff alleges will be instructed on the product's FDA-approved labeling (Compl. ¶¶80, 107, 125, 134, 152, 161, 170, 179).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendants' proposed 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg generic lenalidomide capsule products, for which Defendants filed ANDA No. 210480 with the U.S. Food and Drug Administration (Compl. ¶¶1, 39).
  • Functionality and Market Context: The complaint alleges that Defendants' proposed products are generic versions of Celgene’s REVLIMID® drug product (Compl. ¶1). As such, they are intended to contain the same active ingredient, lenalidomide, and to be therapeutically equivalent for the same medical indications (Compl. ¶¶24, 39). The filing of the ANDA seeks approval to commercially manufacture, use, and sell these generic products in the United States before the expiration of the patents-in-suit, which cover aspects of the REVLIMID® product, its uses, and its distribution system (Compl. ¶¶24, 39).
    No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail to construct a claim chart. The infringement allegations are premised on 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a drug claimed in a patent before the expiration of that patent as a technical act of infringement (Compl. ¶¶44, 53). The complaint alleges that the commercial manufacture, use, or sale of Defendants' Proposed Products after FDA approval will constitute direct infringement under § 271(a) (Compl. ¶¶46, 55), induced infringement under § 271(b) (Compl. ¶¶47, 56), and contributory infringement under § 271(c) (Compl. ¶¶48, 57).

  • Identified Points of Contention:
    • Scope Questions: For the method-of-use patents (e.g., ’517 Patent, ’740 Patent), a question for the court may be whether the indications for which Defendants seek approval in their ANDA, as reflected in their proposed product labeling, will fall within the scope of the patent claims. For the system patents (e.g., ’720 Patent), a question may be whether the drug safety and distribution program Defendants must implement to secure FDA approval will practice the claimed methods.
    • Technical Questions: For the polymorph patents (’800 Patent, ’217 Patent), a central technical question will be whether the specific crystalline form of lenalidomide manufactured by Defendants and formulated in their proposed capsules is the same form as that claimed in the patents. For all asserted patents, the primary point of contention, as signaled by the Defendants' Paragraph IV Certification, will likely be the validity and enforceability of the claims themselves (Compl. ¶42).

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of specific disputed claim terms. However, based on the technology, certain terms may become central to the dispute.

  • For the ’517 Patent (and related method-of-use patents):

    • The Term: "reducing undesirable levels of TNFα"
    • Context and Importance: This phrase from Claim 1 of the ’517 Patent defines the claimed method's purpose and outcome. Practitioners may focus on this term because its construction will determine the scope of diseases covered by the patent. Defendants may argue for a narrow construction tied to the specific examples in the patent, while Plaintiff may argue for a broader meaning covering any condition where TNFα reduction is beneficial.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent's background section lists a wide array of disease conditions linked to TNFα, including endotoxemia, cachexia, arthritis, cerebral malaria, and AIDS, which may support a broad interpretation of "undesirable levels" (’517 Patent, col. 1:24–col. 2:62).
      • Evidence for a Narrower Interpretation: Defendants could argue that the term should be limited by the specific examples and embodiments disclosed, which focus on demonstrating TNFα reduction in a particular assay (’517 Patent, col. 7:22–col. 8:55).

  • For the ’720 Patent (and related system patents):

    • The Term: "patient risk groups"
    • Context and Importance: This term is a key element of the method claimed in now-cancelled Claim 1 and similar claims in related patents. Its definition is critical because the infringement analysis may turn on whether the patient categorization system in Defendants' FDA-mandated REMS program meets the "risk groups" limitation.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification suggests the parameters for defining risk groups "will vary depending upon the drug in question," which may support a flexible, functional definition rather than a rigid structural one (’720 Patent, col. 6:50-54).
      • Evidence for a Narrower Interpretation: The patent provides specific examples of risk groups, such as "female patients of child bearing potential," "sexually active male patients," and "patients to whom administration of the drug may be strictly contraindicated," which could be used to argue for a narrower construction limited to these or similar categorizations (’720 Patent, col. 6:55-65).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement of infringement on the basis that Defendants, upon receiving FDA approval, will "intentionally encourage acts of direct infringement with knowledge of the" patents-in-suit (Compl. ¶¶47, 56). This encouragement would presumably come from product labeling, marketing materials, and instructions to healthcare providers. The complaint alleges contributory infringement on the basis that Defendants' products are "especially adapted for a use that infringes" and that there is "no substantial non-infringing use" for the products (Compl. ¶¶48, 57).
  • Willful Infringement: The complaint does not use the word "willful" but alleges that the case is "an exceptional one" and requests an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶51, 60, 69, etc.). The factual basis for pre-suit knowledge is Defendants' filing of a Paragraph IV certification and sending of a notice letter to Celgene, which demonstrates knowledge of the patents-in-suit (Compl. ¶42).

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

  • A central issue will be one of validity: With sixteen patents asserted, covering the compound, its crystalline forms, its methods of use, and its system of distribution, the case will likely involve a broad challenge to the validity of Celgene's patent estate protecting its REVLIMID® franchise, as previewed by the Defendants' Paragraph IV certification.
  • A key infringement question will be one of system equivalence: For the patents covering the controlled distribution of the drug, the dispute may focus on whether the safety and distribution system Defendants are required to implement to obtain FDA approval for a generic version meets the specific limitations of the claimed methods, particularly in light of claim cancellations in the ’720 Patent resulting from inter partes review.
  • A dispositive technical question for the polymorph patents will be one of physical identity: The infringement analysis for U.S. Patent Nos. 7,465,800 and 7,855,217 will depend on factual evidence, such as X-ray powder diffraction data, establishing whether the crystalline form of lenalidomide in Defendants' proposed generic product is identical to the specific polymorphs claimed.