DCT

1:17-cv-00852

Biogen Intl GmbH v. Glenmark Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00852, D. Del., 06/28/2017
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Glenmark USA is a Delaware corporation, and Defendant Glenmark Ltd. is a foreign corporation subject to suit in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's multiple sclerosis drug, Tecfidera®, constitutes an act of infringement of three U.S. patents.
  • Technical Context: The technology concerns pharmaceutical formulations and methods of using dimethyl fumarate for the treatment of autoimmune diseases, particularly multiple sclerosis.
  • Key Procedural History: This Hatch-Waxman litigation was triggered by Glenmark’s ANDA filing for a generic version of Biogen’s Tecfidera®. The asserted patents are listed in the FDA’s Orange Book. U.S. Patent No. 8,399,514 previously survived an inter partes review (IPR) proceeding in which all asserted claims were found patentable. U.S. Patent Nos. 6,509,376 and 7,320,999 are subject to terminal disclaimers filed in December 2017.

Case Timeline

Date Event
1998-11-19 '376 and '999 Patents Priority Date
2003-01-21 '376 Patent Issue Date
2007-02-08 '514 Patent Priority Date
2008-01-22 '999 Patent Issue Date
2013-03-19 '514 Patent Issue Date
2013-03-27 FDA approves Tecfidera® (NDA No. 204063)
2015-09-28 IPR (IPR2015-01993) filed against '514 Patent
2017-06-02 Glenmark sends Notice Letter to Biogen
2017-06-28 Complaint Filing Date
2018-02-22 IPR Certificate issues, finding claims 1-20 of '514 Patent patentable

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

U.S. Patent No. 6,509,376, Utilization of Dialkyfumarates, issued Jan. 21, 2003

The Invention Explained

  • Problem Addressed: The patent describes the significant disadvantages associated with then-existing immunosuppressive agents used for treating autoimmune diseases and preventing transplant rejection, including the weakening of the body's defenses against infection and an increased risk of malignant diseases (’376 Patent, col. 2:56-64).
  • The Patented Solution: The invention proposes using dialkyl fumarates, such as dimethyl fumarate, in a specific pharmaceutical formulation of "micro-tablets or micro-pellets" (’376 Patent, col. 3:5-13). This formulation is intended to improve gastrointestinal tolerance by releasing the active ingredient in smaller dosages within the intestine, thereby avoiding the local irritation and high concentrations of TNF-α associated with conventional tablets (’376 Patent, col. 5:30-54).
  • Technical Importance: The invention provided a delivery system intended to make oral administration of fumaric acid derivatives more tolerable for patients requiring long-term therapy for chronic conditions like psoriasis and multiple sclerosis (’376 Patent, col. 5:25-29).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶42).
  • The essential elements of Claim 1 are:
    • A pharmaceutical preparation in the form of microtablets or micropellets.
    • The preparation comprises one or more dialkyl fumarates of the recited chemical formula.
    • The preparation includes optionally suitable carriers and excipients.
    • The preparation is for use in transplantation medicine or for the therapy of autoimmune diseases, including polyarthritis and multiple sclerosis.
  • The complaint reserves the right to assert infringement of other claims (Compl. ¶42).

U.S. Patent No. 7,320,999, Dimethyl Fumarate for the Treatment of Multiple Sclerosis, issued Jan. 22, 2008

The Invention Explained

  • Problem Addressed: The patent addresses the same need for safer and more effective treatments for autoimmune diseases, with a specific focus on multiple sclerosis (’999 Patent, col. 4:55-61).
  • The Patented Solution: The invention is a method of treating multiple sclerosis using a pharmaceutical preparation where dimethyl fumarate is the sole active ingredient (’999 Patent, Abstract). By claiming a monotherapy, the patent carves out a specific treatment regimen, distinguished from combination therapies or formulations containing other active compounds (’999 Patent, col. 8:15-20). The specification again notes the advantages of enteric-coated micro-tablet formulations for delivery (’999 Patent, col. 6:30-53).
  • Technical Importance: The patented method defined a specific monotherapy for multiple sclerosis, providing a basis for a treatment regimen using only dimethyl fumarate as the therapeutic agent.

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶56).
  • The essential elements of Claim 1 are:
    • A method of treating multiple sclerosis.
    • The method comprises treating a patient in need of such treatment.
    • The treatment uses an effective amount of a pharmaceutical preparation.
    • The only active ingredient for the treatment of multiple sclerosis present in the preparation is dimethyl fumarate.
  • The complaint reserves the right to assert infringement of other claims (Compl. ¶56).

U.S. Patent No. 8,399,514, Treatment for Multiple Sclerosis, issued March 19, 2013

Technology Synopsis

  • This patent discloses a method of treating multiple sclerosis by administering dimethyl fumarate (DMF) or its metabolite monomethyl fumarate (MMF) to provide a neuroprotective effect (’514 Patent, col. 1:52-62). The core of the invention is the discovery that these compounds activate the Nrf2 cellular pathway, which upregulates cytoprotective genes and provides a therapeutic benefit beyond simple immunomodulation (’514 Patent, col. 2:15-24). The patent, attached as Exhibit C to the complaint, includes a Western blot analysis (Figure 1) purporting to show that DMF and MMF activate the Nrf2 pathway (’514 Patent, Fig. 1; Compl. ¶64).

Asserted Claims

  • At least independent claim 1 (Compl. ¶71).

Accused Features

  • The complaint alleges that Defendant will induce infringement by marketing its generic dimethyl fumarate product with a label that instructs physicians and patients to practice the claimed method, specifically by orally administering a therapeutically effective amount of about 480 mg per day to treat multiple sclerosis (Compl. ¶¶ 74-75).

III. The Accused Instrumentality

Product Identification

  • Defendant’s proposed generic dimethyl fumarate delayed-release capsules, in 120 mg and 240 mg strengths, as described in ANDA No. 210309 (Compl. ¶39).

Functionality and Market Context

  • The accused product is a generic pharmaceutical intended to be a therapeutic equivalent to Plaintiff’s branded drug, Tecfidera® (Compl. ¶¶ 3, 39). It is designed for oral administration for the treatment of relapsing forms of multiple sclerosis (Compl. ¶37). The complaint alleges that Defendant intends to market and sell this product in the United States upon receiving FDA approval, directly competing with Tecfidera® (Compl. ¶¶ 16, 44).

IV. Analysis of Infringement Allegations

'376 Patent 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 does not provide sufficient detail for analysis of the physical form of Defendant's proposed product. N/A col. 8:8-9
...comprising one or more dialkyl fumarates of the formula... Defendant's generic product is a formulation containing dimethyl fumarate, which is a species of dialkyl fumarate. ¶39 col. 8:9-21
...for use in ... the therapy of autoimmune diseases such as ... multiple sclerosis. Defendant's ANDA seeks approval for its product to be used for the treatment of relapsing forms of multiple sclerosis. ¶39 col. 8:22-27

'999 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple sclerosis... Defendant's proposed product label will allegedly instruct physicians and patients to use the product for the treatment of multiple sclerosis. ¶59 col. 8:15
...wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate. Defendant's product is described as "dimethyl fumarate delayed-release capsules," which the complaint alleges will be used in a manner where dimethyl fumarate is the sole active ingredient. ¶39, ¶60 col. 8:17-20

Identified Points of Contention

  • Scope Questions: A central question for the '376 Patent is factual: does the physical formulation of Glenmark's proposed generic product meet the "microtablets or micropellets" limitation of claim 1? The complaint does not contain allegations regarding the specific structure of the accused product. For the '999 Patent, a key legal question may be the scope of "only active ingredient." Does this term preclude any excipient that may have some ancillary biological effect, or does it mean the sole API as defined by FDA regulations?
  • Technical Questions: For all three method-of-use claims ('999 and '514 patents), infringement will depend on a theory of inducement. A key evidentiary question will be whether the final, FDA-approved label for Glenmark's product instructs users to perform the patented methods, thereby inducing infringement by physicians and patients.

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 preparation. As the complaint provides no details on the structure of the accused product, the construction of this term will be dispositive for the literal infringement analysis of the '376 Patent.
  • Intrinsic Evidence for a Broader Interpretation: The specification suggests a size range, stating the "mean diameter... of the pellets or micro-tablets is in the range from 300 to 2,000 µm" (’376 Patent, col. 3:50-52). A party could argue this is an exemplary, not a limiting, range.
  • Intrinsic Evidence for a Narrower Interpretation: The patent repeatedly links this formulation to the technical benefit of improved gastrointestinal tolerance (’376 Patent, col. 5:30-54). A party could argue the term should be construed to require a structure that necessarily achieves this stated advantage. Example 1 describes tablets with a "diameter of 2.0 mm" (2,000 µm), which could be argued to define the upper boundary of the term (’376 Patent, col. 6:32-33).

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

  • Context and Importance: This limitation defines the claimed method as a monotherapy. Its construction is critical because if the accused product is found to contain any other "active ingredient," it would fall outside the claim scope.
  • Intrinsic Evidence for a Broader Interpretation: A party could argue that in the context of pharmaceutical claims, "active ingredient" refers to the Active Pharmaceutical Ingredient (API) as designated for regulatory purposes, allowing for the presence of various inactive excipients.
  • Intrinsic Evidence for a Narrower Interpretation: The specification does not provide an explicit definition. A party could argue for a plain and ordinary meaning, where any component with a pharmacological or biological effect could be considered "active," potentially implicating certain excipients and narrowing the claim scope.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges both induced and contributory infringement for the '999 and '514 patents. Inducement is based on the allegation that Defendant's product label will actively encourage and instruct physicians and patients to use the product in an infringing manner (Compl. ¶¶ 59, 74). Contributory infringement is based on the allegation that the accused product is a material part of the invention and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶ 60, 75).

Willful Infringement

  • The complaint alleges that Defendant has actual knowledge of the patents-in-suit, citing the patents' listing in the FDA's Orange Book and Defendant’s June 2, 2017 Notice Letter (Compl. ¶¶ 41, 55, 70). While these facts may support a willfulness claim, the prayer for relief requests a declaration that the case is "exceptional" for an award of attorney fees under 35 U.S.C. §§ 285 and 271(e)(4), rather than enhanced damages under § 284 (Compl. p. 16, ¶16).

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

  • A central factual issue will be one of "structural correspondence": does the physical formulation of Defendant's proposed generic product, on which the complaint is silent, meet the "microtablets or micropellets" limitation of the '376 patent?
  • A key evidentiary question for the method claims ('999 and '514 patents) will be one of "inducement": will the final, FDA-approved label for Defendant's product contain instructions that direct medical professionals and patients to perform the claimed methods, including the specific "only active ingredient" monotherapy of the '999 patent and the "about 480 mg per day" dosage of the '514 patent?
  • A core legal issue will be one of "definitional scope": how will the court construe the term "only active ingredient" from the '999 patent, and will that construction read on a generic formulation that contains both a designated API and various pharmaceutical excipients?