DCT

1:17-cv-00851

Biogen Intl GmbH v. Cipla Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00851, D. Del., 06/28/2017
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Cipla USA is incorporated in Delaware, and Defendant Cipla Ltd. is an alien corporation that may be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic dimethyl fumarate delayed-release capsules for treating multiple sclerosis constitutes an act of infringement of three patents covering Plaintiff's branded drug, Tecfidera®.
  • Technical Context: The technology relates to pharmaceutical formulations and methods of using dialkyl fumarates, specifically dimethyl fumarate, for the treatment of autoimmune diseases like multiple sclerosis.
  • Key Procedural History: This is a Hatch-Waxman action initiated in response to Cipla’s filing of ANDA No. 210305. The complaint states that Biogen received a Notice Letter from Cipla on May 25, 2017, providing notice of the ANDA filing and a certification against the patents-in-suit, which are listed in the FDA’s Orange Book for Tecfidera®. The complaint notes that the Notice Letter did not allege non-infringement for any of the asserted patents.

Case Timeline

Date Event
1998-11-19 Priority Date for '376 and '999 Patents
2003-01-21 '376 Patent Issued
2007-02-08 Priority Date for '514 Patent
2008-01-22 '999 Patent Issued
2013-03-19 '514 Patent Issued
2013-03-27 FDA Approved NDA No. 204063 (Tecfidera®)
2017-05-25 Biogen Received Notice Letter of ANDA Filing from Cipla
2017-06-28 Complaint Filed

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

U.S. Patent No. 6,509,376 - “Utilization of Dialkyfumarates,” Issued January 21, 2003

The Invention Explained

  • Problem Addressed: The patent describes a need for treatments for autoimmune diseases and organ transplant rejection that lack the severe side effects associated with then-current immunosuppressive agents like cyclosporine (U.S. Patent No. 6,509,376, col. 2:56-64). It notes that high oral doses of fumaric acid derivatives can cause significant gastrointestinal irritation (U.S. Patent No. 6,509,376, col. 5:30-34).
  • The Patented Solution: The invention proposes formulating dialkyl fumarates into enteric-coated micro-tablets or micro-pellets. This formulation is designed to be released gradually in the intestine, avoiding high local concentrations of the active ingredient and thereby reducing gastrointestinal side effects and improving patient tolerance (U.S. Patent No. 6,509,376, col. 5:35-55).
  • Technical Importance: This delivery system was designed to make fumaric acid derivatives, known for their therapeutic potential but also for their side effects, a more viable option for long-term treatment of chronic autoimmune conditions (U.S. Patent No. 6,509,376, Abstract).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶42).
  • Essential elements of claim 1 include:
    • A pharmaceutical preparation in the form of microtablets or micropellets.
    • Comprising one or more dialkyl fumarates according to a specified chemical formula.
    • For use in transplantation medicine or for the therapy of autoimmune diseases.
  • The complaint does not explicitly reserve the right to assert dependent claims but alleges infringement of "at least one claim including at least claim 1" (Compl. ¶42).

U.S. Patent No. 7,320,999 - “Dimethyl Fumarate for the Treatment of Multiple Sclerosis,” Issued January 22, 2008

The Invention Explained

  • Problem Addressed: The patent addresses the same general problem as its parent '376 patent: the need for effective and well-tolerated treatments for autoimmune diseases, but focuses specifically on multiple sclerosis (U.S. Patent No. 7,320,999, col. 4:54-58).
  • The Patented Solution: The invention claims a method of treating multiple sclerosis by administering a pharmaceutical preparation where dimethyl fumarate is the only active ingredient. The specification carries forward the disclosure from the parent patent regarding the use of enteric-coated micro-tablets to improve tolerability (U.S. Patent No. 7,320,999, col. 5:30-55; col. 8:15-20).
  • Technical Importance: This patent narrowed the therapeutic focus from general autoimmune diseases to the specific indication of multiple sclerosis, claiming a monotherapy approach with dimethyl fumarate (U.S. Patent No. 7,320,999, Abstract).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶56).
  • Essential elements of claim 1 include:
    • A method of treating multiple sclerosis.
    • Comprising treating a patient with an effective amount of a pharmaceutical preparation.
    • Wherein the only active ingredient for treating multiple sclerosis in the preparation is dimethyl fumarate.
  • The complaint alleges infringement of "at least one claim including at least claim 1" (Compl. ¶56).

U.S. Patent No. 8,399,514 - “Treatment for Multiple Sclerosis,” Issued March 19, 2013

The Invention Explained

This patent addresses the problem of neuronal damage caused by oxidative stress in neurological diseases like MS (U.S. Patent No. 8,399,514, col. 1:11-20). The invention is a method of treatment that works by activating the Nrf2 cellular pathway, which upregulates cytoprotective genes and provides neuroprotection. The patent identifies dimethyl fumarate (DMF) and its metabolite monomethyl fumarate (MMF) as compounds that can activate this protective pathway (U.S. Patent No. 8,399,514, col. 1:53-62, col. 19:10-15).

Key Claims at a Glance

  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶71).
  • Accused Features: Cipla’s filing of ANDA No. 210305 for generic dimethyl fumarate capsules is alleged to be an act of infringement, with future manufacture, use, and sale also constituting infringement (Compl. ¶¶71-72).

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendants' generic dimethyl fumarate delayed-release capsules, as described in ANDA No. 210305 submitted to the FDA (Compl. ¶39).

Functionality and Market Context

  • The accused products are generic pharmaceuticals containing 120 mg and 240 mg of dimethyl fumarate, intended for the treatment of relapsing forms of multiple sclerosis (Compl. ¶39). The act of infringement alleged in the complaint is the statutory act of filing the ANDA under 35 U.S.C. § 271(e)(2), which seeks FDA approval to market a generic version of Biogen's Tecfidera® before the expiration of the patents-in-suit (Compl. ¶¶ 10, 43, 57, 72).
  • The complaint alleges that Cipla's product, to gain approval as a generic, must have the same active ingredient, dosage form, and strength as Tecfidera®, and its labeling must be the same as the FDA-approved labeling for Tecfidera® (Compl. ¶¶ 59, 74).

IV. Analysis of Infringement Allegations

Figure 1 from the '514 Patent, attached as Exhibit C to the complaint, is a Western blot analysis presented to demonstrate that dimethyl fumarate (DMF) and monomethyl fumarate (MMF) are activators of the Nrf2 protein at various concentrations (Compl. Ex. C, Fig. 1).

U.S. Patent No. 6,509,376 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Pharmaceutical preparation in the form of microtablets or micropellets... The complaint alleges that Defendants' generic products described in ANDA No. 210305, which are intended to be a generic equivalent of Tecfidera®, will meet this limitation. ¶42, ¶43 col. 8:8-9
...comprising one or more dialkyl fumarates of the formula... Defendants' ANDA products contain dimethyl fumarate, which is a dialkyl fumarate covered by the claimed formula. ¶39 col. 8:9-27
...for use in ... therapy of autoimmune diseases... Defendants' ANDA products are for the treatment of multiple sclerosis, which the patent identifies as an autoimmune disease. ¶39 col. 3:55-58

U.S. Patent No. 7,320,999 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple sclerosis comprising treating a patient... The labeling for Defendants' ANDA products will instruct physicians and patients to use the product to treat multiple sclerosis. ¶59, ¶60 col. 8:15-16
...with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis... Defendants' ANDA products are supplied in 120 mg and 240 mg dosages intended to be therapeutically effective for treating MS. ¶39 col. 8:16-18
...wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate. Defendants' ANDA No. 210305 identifies dimethyl fumarate as the active pharmaceutical ingredient for the treatment of MS. ¶39 col. 8:18-20

Identified Points of Contention

  • Scope Questions: For the '376 patent, a central dispute may concern the construction of "microtablets or micropellets." Infringement will depend on whether the specific formulation disclosed in Cipla's confidential ANDA falls within the scope of this term. For the '999 and '514 patents, a question may arise as to whether the specified dosages in the ANDA constitute a "therapeutically effective amount" for performing the claimed methods, which could also raise validity questions under 35 U.S.C. § 112.
  • Technical Questions: For the '514 patent, infringement analysis will likely focus on a question of inherent mechanism. What evidence demonstrates that administering the accused product at the specified doses for treating MS inherently results in the upregulation of the Nrf2 pathway, as the patent claims is the basis for the treatment?

V. Key Claim Terms for Construction

  • The Term: "microtablets or micropellets" (’376 Patent, Claim 1)

    • Context and Importance: This term defines the physical form of the claimed composition. The infringement analysis for the '376 patent will hinge on whether Cipla's formulation, as described in its ANDA, meets the definition of this term.
    • Intrinsic Evidence for a Broader Interpretation: A party may argue that the term should be construed broadly to cover any small, particulate dosage form that achieves the stated goal of gradual intestinal release, as the patent does not provide a restrictive definition in the claims themselves (U.S. Patent No. 6,509,376, col. 8:8-9).
    • Intrinsic Evidence for a Narrower Interpretation: The specification describes embodiments having a "mean diameter ... in the range from 300 to 2,000 µm" and being pressed into "convex tablets," which a party could argue limits the scope of the term to these disclosed characteristics (U.S. Patent No. 6,509,376, col. 3:50-52; col. 6:31-32).

  • The Term: "only active ingredient" (’999 Patent, Claim 1)

    • Context and Importance: This term is critical because it defines the claimed method as a monotherapy. If Cipla's generic product were found to contain another substance that qualifies as an "active ingredient" for treating multiple sclerosis, it could potentially avoid infringement of this claim.
    • Intrinsic Evidence for Interpretation: The patent itself does not define "active ingredient." Practitioners may focus on this term because its interpretation will determine whether excipients or other components of the formulation could negate infringement. A patentee might argue the term refers to the single API (Active Pharmaceutical Ingredient) designated in the ANDA, while a defendant could argue for a broader meaning encompassing any component with a therapeutic effect.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges inducement and contributory infringement of the '999 and '514 method-of-use patents. The inducement claims are based on allegations that Cipla, with knowledge of the patents, will encourage infringement by physicians and patients through its product labeling, which must copy the Tecfidera® label (Compl. ¶¶ 59, 74). The contributory infringement claims are based on allegations that Cipla will sell a product that is a material part of the invention and not a staple article suitable for substantial non-infringing use (Compl. ¶¶ 60, 75).
  • Willful Infringement: The complaint does not use the word "willful," but it alleges Cipla has "actual knowledge" of all three patents-in-suit based on the Notice Letter dated May 25, 2017 (Compl. ¶¶ 41, 55, 70). The prayer for relief also asks the court to declare this an "exceptional case" under 35 U.S.C. § 285, a remedy often associated with a finding of willfulness (Compl. p. 16, ¶16).

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

  • A core issue will be one of claim scope and validity: How will the term "microtablets or micropellets" in the '376 patent be construed, and will Cipla's proposed generic formulation fall within that scope? The layered protection across three patents suggests that even if Cipla can avoid this composition claim, it faces infringement allegations on two distinct method-of-use patents.
  • A key evidentiary question will be one of mechanism of action: For the '514 patent, what evidence will be required to prove that treating MS with the accused generic product inherently performs the claimed method of upregulating the Nrf2 pathway? This question implicates not only infringement but also potential validity challenges related to written description and enablement.
  • A central strategic question involves the interplay of the asserted patents: How has Biogen's strategy of obtaining patents on a composition ('376), a general method of use ('999), and a specific biological mechanism of action ('514) created a "thicket" that complicates a potential generic entrant's ability to design a non-infringing alternative or challenge the entire patent portfolio?