Biogen Intl GmbH v. Par Pharmaceutical Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Biogen International GmbH (Switzerland) and Biogen MA Inc. (Massachusetts)
  • Defendant: Par Pharmaceutical, Inc. (New York)
  • Plaintiff’s Counsel: Ashby & Geddes; Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.
• Case Identification: 1:17-cv-00873, D. Del., 06/30/2017
• Venue Allegations: Plaintiff alleges venue is proper in Delaware because Defendant markets and distributes pharmaceutical products in the district and its Abbreviated New Drug Application (ANDA) filing reliably predicts future activities, including sales, purposefully directed at Delaware.
• Core Dispute: Plaintiff alleges that Defendant’s filing of an ANDA to market a generic version of Plaintiff’s multiple sclerosis drug, Tecfidera®, constitutes an act of infringement of two patents covering methods of using dimethyl fumarate.
• Technical Context: The technology relates to pharmaceutical methods for treating multiple sclerosis, a chronic autoimmune disease of the central nervous system, using specific dosages and formulations of dimethyl fumarate.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 209768 to the FDA and its subsequent Notice of Certification letter to Plaintiff, dated May 24, 2017. Plaintiff notes a concurrent case was filed in New York as a protective measure against potential venue challenges. The patents-in-suit are listed in the FDA’s Orange Book for Tecfidera®. An Inter Partes Review (IPR) was later filed against the ’514 patent (IPR2015-01993), in which all challenged claims were ultimately found patentable.

Case Timeline

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

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 describes the challenge of treating autoimmune diseases, noting that conventional immunosuppressive agents can weaken the body's defenses against infection and increase the risk of malignant diseases (’999 Patent, col. 4:57-59).
• The Patented Solution: The invention claims a method for treating multiple sclerosis by administering a pharmaceutical preparation where dimethyl fumarate is the "only active ingredient" (’999 Patent, col. 8:17-19). This approach is presented as a way to modulate the immune system without the significant side effects associated with prior therapies (’999 Patent, col. 5:45-48). The specification also discusses the benefits of specific formulations, such as enteric-coated micro-tablets, to improve patient tolerance (’999 Patent, col. 6:30-52).
• Technical Importance: The invention claimed a monotherapy for multiple sclerosis using a specific fumaric acid ester, distinguishing it from prior art that involved mixtures of compounds or different therapeutic agents.

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶29).
• Independent Claim 1 requires:
  • A method of treating multiple sclerosis.
  • 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 reserves the right to assert additional claims (Compl. ¶28).

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

The Invention Explained

• Problem Addressed: The patent addresses the need for therapies that not only reduce inflammation in multiple sclerosis but also counter the underlying neuronal damage and axonal loss, which are described as pathologies potentially independent of inflammation (’514 Patent, col. 1:44-46).
• The Patented Solution: The invention discloses a method of treating multiple sclerosis by orally administering a specific daily dose of dimethyl fumarate (DMF) or its metabolite, monomethyl fumarate (MMF). The claimed method centers on a "therapeutically effective amount" that is "about 480 mg per day" (’514 Patent, col. 28:64-65). The specification suggests these compounds may provide a neuroprotective effect by activating the cellular Nrf2 pathway, which defends against oxidative stress (’514 Patent, col. 2:14-18).
• Technical Importance: This patent claims a specific, clinically-relevant dosage regimen for DMF/MMF, moving beyond a general method of use to a defined therapeutic amount for treating multiple sclerosis.

Key Claims at a Glance

• The complaint asserts independent claim 1 (Compl. ¶44).
• Independent Claim 1 requires:
  • A method of treating a subject for multiple sclerosis via oral administration.
  • The administration of a pharmaceutical composition "consisting essentially of" a therapeutically effective amount of DMF, MMF, or a combination thereof, plus excipients.
  • Wherein the therapeutically effective amount is "about 480 mg per day."
• The complaint reserves the right to assert additional claims (Compl. ¶43).

III. The Accused Instrumentality

Product Identification

• Defendant Par's proposed generic dimethyl fumarate delayed-release capsules, containing 120 mg and 240 mg of dimethyl fumarate, as described in ANDA No. 209768 (Compl. ¶25).

Functionality and Market Context

• The accused products are intended to be generic equivalents of Biogen's branded drug, Tecfidera®, which is used to treat relapsing forms of multiple sclerosis (Compl. ¶¶3, 6). As an ANDA product, its approval is contingent on being bioequivalent to Tecfidera®. The complaint alleges that upon approval, Defendant will be required to copy the FDA-approved labeling for Tecfidera®, which instructs on the method of use for treating multiple sclerosis (Compl. ¶¶31, 46).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

• ’999 Patent Infringement Allegations

• ’514 Patent Infringement Allegations

• Identified Points of Contention:
  • Scope Questions: For the ’514 patent, a central dispute may involve the scope of "about 480 mg per day." The parties may contest whether this term covers only the precise 480 mg dose or encompasses a broader range of clinically effective dosages. A second question relates to the term "consisting essentially of," which raises the issue of whether any unlisted ingredients in Defendant's formulation materially alter the basic and novel properties of the claimed invention.
  • Technical Questions: While the complaint’s infringement theory appears direct, particularly given the ANDA context requiring label-copying, disputes not apparent from the complaint, such as patent validity challenges based on obviousness or anticipation, are common in such litigation and may become the central focus.

V. Key Claim Terms for Construction

• ’999 Patent:

  • The Term: "only active ingredient"
  • Context and Importance: This term is critical for defining the composition. Infringement requires that no other ingredient in the formulation qualifies as "active" for treating multiple sclerosis. Practitioners may focus on this term because a defendant in an ANDA case could argue that an excipient possesses a secondary, albeit unapproved, therapeutic effect, thereby avoiding literal infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent does not explicitly define the term, which a party might argue defaults to a plain and ordinary meaning, such as the single ingredient recognized by the FDA as therapeutically active for the indication.
    • Evidence for a Narrower Interpretation: The patent claims a method where the preparation contains dimethyl fumarate as the only active ingredient, distinguishing it from prior art combinations (’999 Patent, col. 8:17-19). This supports a strict reading where any component with a demonstrable pharmacological effect could fall outside the claim.

• ’514 Patent:

  • The Term: "about 480 mg per day"
  • Context and Importance: The definition of "about" is dispositive for determining the scope of the dosage claim. The term's breadth will dictate whether dosages that deviate slightly from 480 mg per day still infringe. Practitioners will focus on this term because its construction could either capture the accused product or render the claim invalid over prior art disclosing similar dosage ranges.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes a wider dosage range, stating an effective dose "can be from about 0.1 g to 1 g per day," and more specifically "from about 240 mg to about 720 mg per day" (’514 Patent, col. 18:59-62). This language may support an interpretation where "about 480 mg" is not rigidly fixed.
    • Evidence for a Narrower Interpretation: The number "480" is highly specific and corresponds to a clinically tested regimen (240 mg twice daily). A party could argue that such precision implies "about" should be construed very narrowly around that specific value, not as a proxy for a broad range.

VI. Other Allegations

• Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. Inducement is premised on the allegation that Defendant, by copying the FDA-approved Tecfidera® label as required by law, will actively encourage and instruct physicians and patients to use the generic product in an infringing manner (Compl. ¶¶31, 46). Contributory infringement is based on allegations that the product is a material part of the invention and is not a staple article suitable for substantial non-infringing use (Compl. ¶¶32, 47).
• Willful Infringement: The complaint does not use the term "willful infringement," but it pleads facts that could support such a claim. It alleges Defendant has "actual knowledge" of the patents-in-suit based on its receipt of a Notice of Certification letter prior to the lawsuit's filing (Compl. ¶¶27, 42). Furthermore, the prayer for relief requests that the case be declared "exceptional" under 35 U.S.C. § 285, a remedy often tied to findings of willfulness (Compl. p. 11, item 11).

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

• A central issue for the ’514 patent will be one of claim scope: How will the court construe the term "about 480 mg per day"? Whether it is interpreted as a precise figure or a flexible range will be critical to both infringement and validity analyses, as a broader construction could increase the likelihood of encompassing prior art.
• The primary battleground, typical for ANDA litigation, will likely be over patent validity. While not detailed in the complaint, a key question for the court will be whether the claimed inventions were obvious. Specifically, for the ’999 patent, was it obvious to use dimethyl fumarate as a monotherapy for MS, and for the ’514 patent, was arriving at the 480 mg/day dosage an obvious step for a person of ordinary skill?
• A third question concerns induced infringement: Assuming the patents are valid, does the proposed label for the generic product, which must mirror the innovator’s label, contain sufficient instruction to meet the legal standard for inducing infringement by directing physicians and patients to practice the patented methods?