DCT

1:17-cv-00824

Biogen Intl GmbH v. Aurobindo Pharma USA Inc

Log In
Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00824, D. Del., 06/26/2017
  • Venue Allegations: Venue is based on Defendant entities being incorporated in the State of Delaware.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for generic dimethyl fumarate capsules constitutes an act of infringement of two patents covering methods of using the compound to treat multiple sclerosis, which is marketed by Plaintiff as Tecfidera®.
  • Technical Context: The technology involves the use of dimethyl fumarate, a fumaric acid ester, as an oral therapeutic for multiple sclerosis, a chronic autoimmune disease that affects the central nervous system.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff’s receipt of a notice letter from Defendant concerning its ANDA filing. The complaint alleges that this notice letter did not contain an allegation of non-infringement for either of the asserted patents. U.S. Patent No. 8,399,514 was the subject of an Inter Partes Review (IPR2015-01993), which concluded with a certificate issued on February 22, 2018, confirming the patentability of claims 1-20. U.S. Patent No. 7,320,999 is subject to a terminal disclaimer filed on December 14, 2017.

Case Timeline

Date Event
1998-11-19 ’999 Patent Priority 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 NDA for Tecfidera® (dimethyl fumarate)
2015-09-28 Inter Partes Review (IPR2015-01993) filed for ’514 Patent
2017-05-24 Plaintiff receives Defendant's notice letter regarding ANDA filing
2017-06-26 Complaint Filing Date
2018-02-22 IPR Certificate issued confirming patentability of ’514 Patent claims

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 state of treatment for autoimmune diseases and organ transplantation, noting that conventional immunosuppressive agents present significant risks, including weakening the body's defense against infectious diseases and increasing the risk of malignancies (’999 Patent, col. 4:56-59).
  • The Patented Solution: The invention proposes using certain dialkyl fumarates—specifically dimethyl fumarate—as the sole active therapeutic agent for treating autoimmune diseases, including multiple sclerosis (’999 Patent, col. 5:3-6; col. 8:14-20). The specification suggests that this approach can modulate the immune system effectively while avoiding the disadvantages of prior therapies, and it highlights the use of formulations like enteric-coated micro-tablets to improve gastrointestinal tolerance and resorption (’999 Patent, col. 6:30-52).
  • Technical Importance: The patent describes a therapeutic method for multiple sclerosis using an active ingredient with a different mechanism and side-effect profile compared to many existing immunosuppressants of the time (’999 Patent, col. 4:60-67).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶36).
  • The essential elements of independent claim 1 are:
    • A method of treating multiple sclerosis
    • comprising treating a patient in need... with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis
    • wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate
  • The complaint reserves the right to assert other claims (Compl. ¶36).

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

The Invention Explained

  • Problem Addressed: The patent identifies oxidative stress from reactive oxygen/nitrogen species (ROS/RNS) as a key driver of neuronal damage in neurodegenerative diseases like multiple sclerosis (’514 Patent, col. 1:62-col. 2:2). It notes that while some compounds were known to be neuroprotective, their precise mechanism of action was not well understood (’514 Patent, col. 2:35-39).
  • The Patented Solution: The invention is based on the discovery that fumaric acid derivatives like dimethyl fumarate (DMF) and its metabolite monomethyl fumarate (MMF) provide neuroprotection by activating the Nrf2 (Nuclear factor E2-related factor 2) cellular stress-response pathway (’514 Patent, col. 5:11-20, Fig. 1). By claiming a specific oral dosage regimen, the patent leverages this mechanistic understanding to provide a defined method of treatment for MS (’514 Patent, Abstract; col. 28:57-68).
  • Technical Importance: This patent provided an asserted biochemical mechanism—Nrf2 pathway activation—for the therapeutic effect of dimethyl fumarate in MS, distinguishing it from general immunosuppression and claiming a specific daily dosage (’514 Patent, col. 1:15-18).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶52).
  • The essential elements of independent claim 1 are:
    • A method of treating a subject in need of treatment for multiple sclerosis
    • comprising orally administering... a pharmaceutical composition consisting essentially of:
    • (a) a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, and
    • (b) one or more pharmaceutically acceptable excipients
    • wherein the therapeutically effective amount... is about 480 mg per day
  • The complaint reserves the right to assert other claims (Compl. ¶52).

III. The Accused Instrumentality

  • Product Identification: Defendant's proposed generic dimethyl fumarate delayed-release capsules, containing 120 mg and 240 mg of dimethyl fumarate, as described in Abbreviated New Drug Application (ANDA) No. 21-0385 (Compl. ¶¶8, 33).
  • Functionality and Market Context: The accused instrumentality is the filing of an ANDA, which is a technical act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶37, ¶53). The complaint alleges that the product described in the ANDA is a generic version of Plaintiff's Tecfidera® product and is intended for the treatment of relapsing forms of multiple sclerosis (Compl. ¶3). It is further alleged that Defendant's product, if approved, would be sold with a label that copies the Tecfidera® label, thereby instructing physicians and patients to use the product in a manner that directly infringes the asserted patents (Compl. ¶40, ¶55).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’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 ANDA seeks approval for a product specifically for the treatment of multiple sclerosis, and its proposed label will instruct this use. ¶37 col. 8:14-15
...wherein the only active ingredient... present in said pharmaceutical preparation is dimethyl fumarate. The product described in Defendant's ANDA is alleged to contain dimethyl fumarate as its sole active pharmaceutical ingredient. ¶33 col. 8:17-20
  • Identified Points of Contention:
    • Scope Questions: A potential dispute may center on the meaning of "only active ingredient." The question could be raised whether any excipients in the Defendant's formulation could be characterized as having a therapeutic effect, thereby taking the product outside the literal scope of the claim.

’514 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating... multiple sclerosis comprising orally administering... a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate... Defendant's ANDA describes an oral dimethyl fumarate capsule for treating multiple sclerosis. ¶53 col. 28:57-63
...wherein the therapeutically effective amount... is about 480 mg per day. The complaint alleges that Defendant's product, if approved, will be administered according to a label instructing a dosage of about 480 mg per day, in line with the established regimen for the reference listed drug, Tecfidera®. ¶55 col. 28:66-68
  • Identified Points of Contention:
    • Scope Questions: The construction of "consisting essentially of" may be a central issue. This raises the question of whether any inactive ingredients in Defendant's formulation materially affect the "basic and novel properties" of the claimed invention, which the patent links to Nrf2 pathway activation (’514 Patent, col. 5:11-14).
    • Technical Questions: A factual dispute could arise over the dosage. The term "about 480 mg per day" raises the question of what numerical range this encompasses and whether the dosing instructions on Defendant's proposed label fall within that scope.

V. Key Claim Terms for Construction

For the ’999 Patent

  • The Term: "only active ingredient"
  • Context and Importance: This term defines the composition of the therapeutic preparation. Its construction is critical because if Defendant's formulation is found to contain any other substance that qualifies as an "active ingredient," it would not infringe this claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A party could argue the term refers to the substance formally designated as the Active Pharmaceutical Ingredient (API) under FDA regulatory standards, allowing for the presence of standard excipients without therapeutic properties. The patent itself lists numerous common excipients (’999 Patent, col. 6:17-29).
    • Evidence for a Narrower Interpretation: The specification's repeated focus on dialkyl fumarates and the problems with combination therapies could support a construction that strictly forbids any other substance with a known or inherent therapeutic effect, regardless of its regulatory classification (’999 Patent, Abstract; col. 5:46-55).

For the ’514 Patent

  • The Term: "consisting essentially of"
  • Context and Importance: This is a term of art that permits the presence of unlisted ingredients that do not materially affect the basic and novel properties of the invention. Practitioners may focus on this term because the infringement analysis will depend on whether any excipients in Defendant's generic formulation are found to materially alter the claimed invention's neuroprotective function.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification's inclusion of "(b) one or more pharmaceutically acceptable excipients" within the "consisting essentially of" clause itself suggests the inventors contemplated the inclusion of standard inactive ingredients without nullifying the claim (’514 Patent, col. 28:64-65).
    • Evidence for a Narrower Interpretation: The patent extensively details the Nrf2 activation pathway as the core of the invention (’514 Patent, col. 5:11-20). A party could argue that any excipient that interferes with or independently affects this specific biochemical pathway would be a material alteration, thus placing the formulation outside the claim's scope.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for both patents. Inducement is alleged on the basis that Defendant, upon approval, will market its generic product with a label that instructs physicians and patients to practice the patented methods of treatment (Compl. ¶¶40, 55). Contributory infringement is alleged on the grounds that Defendant's product is a material part of the invention, is not a staple article of commerce, and has no substantial non-infringing uses (Compl. ¶¶41, 56).
  • Willful Infringement: The complaint does not explicitly use the term "willful infringement," but it lays a foundation for such a claim by asserting that Defendant has had "actual knowledge" of the ’999 and ’514 patents since at least May 24, 2017, the date Plaintiff received notice letters (Compl. ¶¶35, 51). The prayer for relief requests that the court declare this an "exceptional case" under 35 U.S.C. § 285, which allows for the award of attorney fees (Compl. p. 13, ¶11).

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

  • A core issue will be one of patent validity: Although not detailed in the complaint, the central dispute in this ANDA case will likely be whether the asserted claims of the ’999 and ’514 patents are valid over the prior art. The successful defense of the ’514 patent in an IPR proceeding may strengthen Plaintiff's position on that patent, but validity will be newly litigated in this forum.
  • A second key issue will be one of claim construction: The outcome may depend on how the court construes the scope-defining terms. For the ’999 patent, what is the boundary of "only active ingredient"? For the ’514 patent, does Defendant's formulation meet the "consisting essentially of" limitation, and does its proposed dosage fall within the scope of "about 480 mg per day"?
  • A final question will be inducement: Assuming the claims are construed to cover the intended use, a dispositive question will be whether Defendant's proposed product label will inevitably lead physicians and patients to carry out the patented methods, thereby making Defendant liable for inducing infringement.