DCT

2:18-cv-00461

Celgene Corp v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:18-cv-00461, D.N.J., 01/11/2018
  • Venue Allegations: Plaintiff alleges venue is proper in the District of New Jersey because Defendant conducts substantial business in the state, including the marketing and sale of pharmaceutical products, and that New Jersey will be a destination for the accused generic drug product.
  • Core Dispute: Plaintiff alleges that Defendant’s 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 nine U.S. patents.
  • Technical Context: The patents-in-suit relate to methods for the controlled distribution of potentially hazardous drugs, specific crystalline forms (polymorphs) of the active ingredient lenalidomide, and methods for using lenalidomide to treat certain cancers.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 211022 and its associated Paragraph IV Certification, which asserted that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic products.

Case Timeline

Date Event
2000-10-23 Priority Date for ’720, ’977, ’784, ’886, and ’531 Patents
2001-11-13 U.S. Patent No. 6,315,720 Issued
2002-11-06 Priority Date for ’363 Patent
2003-05-13 U.S. Patent No. 6,561,977 Issued
2003-09-04 Priority Date for ’800 and ’217 Patents
2004-06-29 U.S. Patent No. 6,755,784 Issued
2006-08-03 Priority Date for ’929 Patent
2008-12-16 U.S. Patent No. 7,465,800 Issued
2008-12-23 U.S. Patent No. 7,468,363 Issued
2010-12-21 U.S. Patent No. 7,855,217 Issued
2012-11-20 U.S. Patent No. 8,315,886 Issued
2014-01-07 U.S. Patent No. 8,626,531 Issued
2014-06-03 U.S. Patent No. 8,741,929 Issued
2017-11-28 Earliest date Defendant sent Paragraph IV Notice Letter
2018-01-11 Complaint Filed

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

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," Issued November 13, 2001

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of distributing beneficial drugs that carry significant risks, such as teratogenic drugs (e.g., thalidomide), which can cause severe birth defects. The background highlights the need for a robust system to prevent contraindicated individuals from receiving such drugs while ensuring access for appropriate patients. (ʼ720 Patent, col. 1:19-34; col. 2:39-49).
  • The Patented Solution: The invention proposes a method for controlled drug delivery where prescriptions are filled only after consulting a "computer readable storage medium" (i.e., a database). This consultation verifies that the prescriber, pharmacy, and patient are all registered and approved. A core feature is the assignment of patients to different "risk groups" based on predefined parameters, which then dictates the type of additional information (e.g., surveys, diagnostic tests) required before dispensing is authorized. ('720 Patent, Abstract; col. 3:1-7).
  • Technical Importance: This systematic, computer-implemented approach provided a verifiable and auditable framework for managing the significant risks associated with drugs like thalidomide and its analogs, a prerequisite for gaining regulatory approval to market them for new indications. (Compl. ¶¶ 14, 16).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specification (Compl. ¶ 33). Independent claim 1 is representative of the invention.
  • Essential elements of Claim 1:
    • Defining a plurality of patient risk groups based on a predefined set of risk parameters for the drug.
    • Defining a set of information to be obtained from the patient, which is probative of the risk of the adverse side effect.
    • In response to the information, assigning the patient to at least one of the risk groups and entering the assignment in the medium.
    • Determining, based on the information and risk group, whether the risk of the adverse side effect is acceptable.
    • Upon determining the risk is acceptable, generating a prescription approval code to be retrieved by the pharmacy before the prescription is filled.
  • The complaint does not explicitly reserve the right to assert dependent claims, but the broad allegation of infringing "one or more claims" implicitly includes them (Compl. ¶ 33).

U.S. Patent No. 6,561,977 - "Methods for delivering a drug to a patient while restricting access to the drug by patients for whom the drug may be contraindicated," Issued May 13, 2003

The Invention Explained

  • Problem Addressed: The patent, a continuation of the application leading to the ’720 Patent, addresses the same technical problem: safely managing the distribution of potentially hazardous drugs to prevent their use by contraindicated patients, such as pregnant women. ('977 Patent, col. 1:21-38).
  • The Patented Solution: The invention claims a method for delivering a drug where pharmacies are permitted to fill prescriptions only after retrieving a "prescription approval code" from a computer readable storage medium. The generation of this code is contingent upon prior registration of the patient and prescriber, assignment of the patient to a risk group, and a determination that the risk of an adverse side effect is acceptable based on information obtained from the patient. ('977 Patent, Abstract; col. 3:11-col. 4:4).
  • Technical Importance: This patent further solidifies the intellectual property protection for the risk management system required by the FDA for drugs like REVLIMID®, known as a Risk Evaluation and Mitigation Strategy (REMS). (Compl. ¶¶ 14, 16).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims without specification (Compl. ¶ 42). Independent claim 1 is representative of the invention.
  • Essential elements of Claim 1:
    • A method permitting prescriptions to be filled only after a pharmacy retrieves a prescription approval code from a computer readable storage medium.
    • The code generation involves defining patient risk groups, defining a set of information to be obtained from a patient probative of risk, assigning the patient to a risk group and entering this in the medium.
    • Determining, based on the information and risk group, whether the risk of the adverse side effect is acceptable.
    • Generating the approval code upon determining the risk is acceptable.
  • The complaint's broad infringement allegation implicitly includes dependent claims (Compl. ¶ 42).

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

  • Patent Identification: These patents, titled "Methods for delivering a drug to a patient while restricting access to the drug by patients for whom the drug may be contraindicated," issued between 2004 and 2014, are part of the same patent family as the ’720 and ’977 patents. (Compl. ¶¶ 6-8).
  • Technology Synopsis: These patents continue to describe and claim computer-implemented systems and methods for the controlled distribution of drugs with known adverse side effects. The core of the invention remains the use of a centralized database, registration of all parties (prescriber, patient, pharmacy), and the use of an authorization or approval code to ensure safety protocols are met before a drug is dispensed. (See, e.g., '784 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more unspecified claims of each patent (Compl. ¶¶ 51, 60, 69).
  • Accused Features: The act of filing an ANDA for a generic version of REVLIMID® is alleged to infringe, as the product could not be marketed without an FDA-mandated REMS program that would practice the patented methods (Compl. ¶¶ 1, 16).

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

  • Patent Identification: Both patents are titled "Polymorphic Forms of 3-(4-amino-1-oxo-1,3 dihydro-isoindol-2-yl)-piperidine-2,6-dione," issued in 2008 and 2010 respectively. (Compl. ¶¶ 9-10).
  • Technology Synopsis: These patents do not cover a method, but rather specific solid crystalline forms (polymorphs) of the active pharmaceutical ingredient lenalidomide. Different polymorphs of a drug can have different physical properties, such as stability and solubility, which are critical for manufacturing and therapeutic efficacy. The patents claim specific polymorphs defined by their characteristic analytical data, such as X-ray powder diffraction (XRPD) patterns. (See, e.g., '800 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more unspecified claims of each patent (Compl. ¶¶ 78, 87).
  • Accused Features: The generic lenalidomide product described in Apotex's ANDA is alleged to be, or contain, the specific polymorphs of lenalidomide claimed in these patents (Compl. ¶ 14).

Multi-Patent Capsule: U.S. Patent Nos. 7,468,363; 8,741,929

  • Patent Identification: U.S. Patent No. 7,468,363, "Methods for treatment of cancers using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione," and U.S. Patent No. 8,741,929, "Methods using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione for the treatment of mantle cell lymphomas," issued in 2008 and 2014. (Compl. ¶¶ 11-12).
  • Technology Synopsis: These patents claim methods of treating specific diseases by administering lenalidomide. The '363 Patent claims methods for treating various cancers, while the '929 Patent is directed more specifically to treating mantle cell lymphomas. The claims typically cover administering a therapeutically effective amount of the compound. (See, e.g., '363 Patent, Abstract).
  • Asserted Claims: The complaint alleges infringement of one or more unspecified claims of each patent (Compl. ¶¶ 96, 105).
  • Accused Features: Apotex's proposed generic product, via its FDA-required labeling, is alleged to instruct and encourage physicians and patients to use the product for the patented treatment methods, which would constitute induced infringement (Compl. ¶ 16).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are the generic 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg lenalidomide drug products described in Apotex's ANDA No. 211022 ("Apotex's ANDA Products") (Compl. ¶ 1).

Functionality and Market Context

The filing of the ANDA is the statutory act of infringement, seeking FDA approval to commercially manufacture, use, and sell a generic version of Celgene’s REVLIMID® drug product prior to the expiration of the patents-in-suit (Compl. ¶ 1, 28). REVLIMID® is a significant biopharmaceutical product for treating cancer, and the accused products are intended to be therapeutic equivalents sold at a lower price point (Compl. ¶ 2, 13). The complaint alleges that the labeling for REVLIMID®, which any generic version would substantially copy, instructs and encourages administration according to the patented methods (Compl. ¶ 16).
No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or specific factual allegations mapping the accused products to the elements of any asserted claims. The infringement theory is based on the act of filing the ANDA under 35 U.S.C. § 271(e)(2). The following tables summarize the apparent, though unstated, infringement theory for the two lead patents.

6,315,720 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
defining a plurality of patient risk groups...; defining a set of information to be obtained from said patient...; assigning said patient to at least one of said risk groups... The filing of an ANDA for a product that will require an FDA-mandated Risk Evaluation and Mitigation Strategy (REMS), which will necessarily involve classifying patients and collecting safety information to manage the drug's known teratogenic risks. ¶1, 16, 33 col. 2:60-3:2
generating a prescription approval code to be retrieved by said pharmacy before said prescription is filled. The future generic REMS program will allegedly include a centralized authorization system that provides an approval to the pharmacy before the drug can be dispensed to an eligible patient. ¶16, 33, 36 col. 4:43-48

6,561,977 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for delivering a drug to patients in need of the drug, while restricting access to the drug by patients for whom the drug may be contraindicated... The filing of an ANDA for a generic version of REVLIMID®, a drug known to be contraindicated in certain patients (e.g., pregnant women), which will be subject to a restricted distribution program. ¶1, 16, 42 col. 3:56-62
permitting prescriptions for the drug to be filled by a pharmacy only after the pharmacy has retrieved an approval code for the prescription from a computer readable storage medium... The required REMS program for the generic product will allegedly operate by requiring pharmacies to obtain authorization from a computer-based system before dispensing the drug, thereby practicing the claimed method. ¶16, 42, 45 col. 4:4-10

Identified Points of Contention

  • Scope Questions: A central question for the system patents (’720, ’977, etc.) will be whether the specific architecture and steps of the REMS program Apotex ultimately implements for its generic product will meet every limitation of the asserted claims. For example, does the term "prescription approval code" as used in the patents read on the specific authorization mechanism Apotex plans to use? The complaint does not describe Apotex's proposed REMS, raising the question of how Celgene will prove it will be infringing.
  • Technical Questions: For the polymorph patents (’800 and ’217), the dispute may turn on detailed analytical chemistry. A key question will be whether the crystalline form of lenalidomide in Apotex's ANDA product exhibits an X-ray powder diffraction pattern with peaks at the angles required by the claims. The complaint provides no analytical data, alleging infringement only "on information and belief" (Compl. ¶ 14).

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail to identify specific claim terms that are in dispute. However, based on the technology of the system patents (’720 and ’977), the construction of the following terms may be critical.

  • The Term: "computer readable storage medium"

    • Context and Importance: This term defines the core technological component of the patented drug distribution system. Practitioners may focus on this term because its scope could determine whether a modern, distributed, or cloud-based REMS architecture falls within the claims of patents filed in the early 2000s, which may have contemplated a more centralized database structure.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification describes the medium in functional terms as a place where registration information for the prescriber, pharmacy, and patient is entered and consulted, without limiting it to a specific hardware configuration (ʼ720 Patent, col. 4:43-48; col. 5:6-10). This may support a construction covering any system that performs these functions.
      • Evidence for a Narrower Interpretation: The description of forwarding registration cards to a "manufacturer or distributor of the drug, or other authorized recipient" for entry could suggest a centralized system managed by a single entity, potentially narrowing the term to exclude more decentralized or federated database models ('720 Patent, col. 6:18-23).

  • The Term: "prescription approval code"

    • Context and Importance: This term describes the gatekeeping mechanism that allows a pharmacy to dispense the drug. The infringement analysis may hinge on whether Apotex's planned authorization process constitutes a "code" as understood in the patent.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent describes the code functionally as something "retrieved" by the pharmacy that provides "approval to dispense the drug," suggesting it could encompass any form of electronic authorization or token ('720 Patent, col. 13:42-47).
      • Evidence for a Narrower Interpretation: The term "code" itself may imply a specific string of characters or numbers, which could support an argument that a different form of electronic verification (e.g., a digital certificate or a status flag in a database) does not meet this limitation. The patent does not provide a specific definition or example of the code's format.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for all nine patents-in-suit. The allegations are based on the premise that Apotex, with knowledge of the patents, will market its generic product with labeling that encourages and instructs physicians and patients to perform the patented methods of treatment and administration (Compl. ¶ 16, 36, 45, 54, 63, 72, 81, 90, 99, 108).
  • Willful Infringement: The complaint does not use the word "willful," but for each patent it alleges the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285 (Compl. ¶ 40, 49, 58, 67, 76, 85, 94, 103, 112). The factual basis for this appears to be Apotex's knowledge of the patents, at least as of its Paragraph IV certification notice letter dated November 28, 2017 (Compl. ¶ 31).

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

  • A core issue will be one of infringement by design: Will the Risk Evaluation and Mitigation Strategy (REMS) program that Apotex is required by the FDA to implement necessarily practice the specific, multi-step registration and authorization methods claimed in Celgene's system patents, or can Apotex successfully design a non-infringing alternative REMS that still satisfies regulatory requirements?
  • A key evidentiary question will be one of physical identity: What analytical evidence will be presented to determine if the crystalline structure of the lenalidomide active ingredient in Apotex’s proposed product is identical to the specific polymorphs claimed in the ’800 and ’217 patents, and how will the parties dispute the interpretation of that scientific data?
  • The case will also present a question of induced infringement: Will Apotex’s proposed product labeling be found to contain sufficient instruction and encouragement to directly lead physicians to prescribe the drug for the specific cancer treatments claimed in the method-of-use patents, thereby establishing the requisite intent for inducement?