DCT

1:17-cv-00116

Biogen Intl GmbH v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00116, N.D. W. Va., 06/30/2017
  • Venue Allegations: Venue is alleged to be proper in the Northern District of West Virginia because the defendant, Mylan Pharmaceuticals Inc, is incorporated in West Virginia.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s Tecfidera® product constitutes infringement of six patents related to dimethyl fumarate formulations and methods for treating multiple sclerosis.
  • Technical Context: The technology concerns oral pharmaceutical formulations of dimethyl fumarate, an immunomodulatory agent used for treating relapsing forms of multiple sclerosis, a chronic autoimmune disease affecting the central nervous system.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 210531 and issuance of a notice letter to Plaintiff on June 1, 2017. The complaint notes that this notice letter did not allege non-infringement of the asserted patents. The patents-in-suit are listed in the U.S. Food and Drug Administration's "Orange Book" as covering Plaintiff's approved drug, Tecfidera®. Several of the asserted patents are subject to terminal disclaimers, tying their expiration dates to earlier patents in the family, which may have implications for the duration of any potential injunctive relief.

Case Timeline

Date Event
1998-11-19 Earliest Priority Date for '376, '999, '001, '840, '393 Patents
2003-01-21 U.S. Patent No. 6,509,376 Issues
2007-02-08 Priority Date for '514 Patent
2008-01-22 U.S. Patent No. 7,320,999 Issues
2009-11-17 U.S. Patent No. 7,619,001 Issues
2010-09-28 U.S. Patent No. 7,803,840 Issues
2013-03-19 U.S. Patent No. 8,399,514 Issues
2013-03-27 FDA approves NDA for Tecfidera® (dimethyl fumarate)
2014-06-24 U.S. Patent No. 8,759,393 Issues
2017-06-01 Plaintiff receives Defendant’s ANDA Notice Letter
2017-06-30 Complaint for Patent Infringement 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 the significant drawbacks of conventional immunosuppressive agents used for autoimmune diseases and in transplantation medicine, including the weakening of the body's defense against infections 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, formulated into enteric-coated micro-tablets or micropellets. This specific delivery system is designed to improve tolerance and reduce gastrointestinal side effects by allowing the drug to be released in smaller, distributed doses within the intestine, thereby avoiding the high local concentrations that cause irritation (’376 Patent, Abstract; col. 4:30-54).
  • Technical Importance: This formulation technology provided a potential pathway for the oral administration of fumaric acid derivatives for serious autoimmune diseases by mitigating the severe side effects and toxicity that had previously limited their therapeutic use (’376 Patent, col. 3:20-30).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶23).
  • Essential elements of claim 1 include:
    • A pharmaceutical preparation in the form of microtablets or micropellets
    • Comprising one or more dialkyl fumarates of a specified chemical formula
    • For use in transplantation medicine or for the therapy of autoimmune diseases, including multiple sclerosis
  • The complaint does not explicitly reserve the right to assert dependent claims.

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, which shares its specification with the ’376 patent, addresses the need for effective treatments for autoimmune diseases like multiple sclerosis that do not carry the severe side effects associated with traditional immunosuppressants (’999 Patent, col. 2:56-64).
  • The Patented Solution: This invention claims a specific method for treating multiple sclerosis. The method involves administering a pharmaceutical preparation where dimethyl fumarate is the sole active ingredient for treating the disease. The patent emphasizes the use of specific formulations, such as enteric-coated microtablets, to achieve this therapeutic effect with improved tolerance (’999 Patent, Abstract; col. 8:14-21).
  • Technical Importance: The invention claims a targeted monotherapy for multiple sclerosis using a specific formulation of dimethyl fumarate, distinguishing it from broader combination therapies or uses for other diseases, and focusing on a single, well-tolerated active agent for a specific neurological condition (’999 Patent, col. 3:5-9).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶37).
  • 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 the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 7,619,001 - Utilization of Dialkylfumarates, issued November 17, 2009

  • Technology Synopsis: This patent, from the same family as the ’376 and ’999 patents, claims a method for treating multiple sclerosis by administering a pharmaceutical preparation that comprises a combination of dimethyl fumarate and its metabolite, methyl hydrogen fumarate (’001 Patent, Abstract; col. 7:61-col. 8:1). The invention contemplates the in-vivo conversion of dimethyl fumarate into its active metabolite as part of the therapeutic process.
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶52).
  • Accused Features: The accused instrumentality is Mylan's proposed generic dimethyl fumarate product, which, upon administration, would be metabolized in the body to form methyl hydrogen fumarate, thus allegedly practicing the claimed method (Compl. ¶52).

U.S. Patent No. 7,803,840 - Utilization of Dialkylfumarates, issued September 28, 2010

  • Technology Synopsis: Also from the same family, this patent claims a method of treating specific autoimmune diseases, including multiple sclerosis, with a pharmaceutical preparation in which dimethyl fumarate is the only active ingredient. The preparation is specified to be in the form of enteric-coated microtablets (’840 Patent, Abstract; col. 8:30-41).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶67).
  • Accused Features: The complaint alleges that Mylan's ANDA product, a generic dimethyl fumarate formulation for MS, will be used in a manner that directly infringes the claimed method (Compl. ¶67).

U.S. Patent No. 8,759,393 - Utilization of Dialkylfumarates, issued June 24, 2014

  • Technology Synopsis: This patent claims a pharmaceutical composition, rather than a method. The claimed composition is in the form of enteric-coated microtablets containing 10 mg to 300 mg of dimethyl fumarate as the sole active ingredient, with a mean diameter of about 2,000 µm (’393 Patent, Abstract; col. 8:20-56).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶82).
  • Accused Features: Mylan's generic dimethyl fumarate delayed-release capsules are alleged to be, or contain, the claimed pharmaceutical preparation (Compl. ¶¶82-83).

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

  • Technology Synopsis: This patent claims a method of treating a subject for multiple sclerosis by orally administering a pharmaceutical composition consisting essentially of a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, where the effective amount is about 480 mg per day (’514 Patent, col. 28:59-67). The invention is directed to a specific, clinically determined effective dosage regimen.
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶95).
  • Accused Features: Mylan’s ANDA product is alleged to infringe because its proposed labeling will instruct administration at the claimed 480 mg/day dosage to achieve bioequivalence with Tecfidera® (Compl. ¶¶95-96, 98).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendant Mylan’s proposed generic drug product described in Abbreviated New Drug Application (ANDA) No. 210531, identified as "dimethyl fumarate delayed-release capsules containing 120 mg and 240 mg of dimethyl fumarate" (Compl. ¶20).

Functionality and Market Context

  • The product is a generic equivalent of Plaintiff’s branded drug, Tecfidera®, which is FDA-approved for the "treatment of relapsing forms of multiple sclerosis" (Compl. ¶¶3, 18). As an ANDA product, it is intended to be therapeutically equivalent and administered according to the same dosage and for the same indication as the reference listed drug. The act of infringement alleged under 35 U.S.C. § 271(e)(2)(A) is the submission of the ANDA itself, seeking FDA approval to market this product prior to the expiration of the patents-in-suit (Compl. ¶24).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

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

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical preparation in the form of microtablets or micropellets The complaint identifies the accused product as "dimethyl fumarate delayed-release capsules." It does not provide specific details on the internal formulation of these capsules (Compl. ¶20). ¶20 col. 7:51-53
comprising one or more dialkyl fumarates of the formula... The accused product contains "dimethyl fumarate," which is a species of dialkyl fumarate covered by the claimed formula (Compl. ¶20). ¶20 col. 8:14-29
for use in...the therapy of autoimmune diseases such as polyarthritis, multiple sclerosis, juvenile-onset diabetes...and enteritis regionalis Crohn. The ANDA seeks approval for a product to treat "relapsing forms of multiple sclerosis," an enumerated autoimmune disease in the claim (Compl. ¶¶3, 6, 18). ¶¶3, 6, 18 col. 8:14-29
  • Identified Points of Contention:
    • Scope Questions: A primary question may be whether Defendant’s "delayed-release capsules" meet the claim limitation "in the form of microtablets or micropellets." The infringement analysis will depend on the specific formulation disclosed in the ANDA, which is not detailed in the complaint. This raises the question of whether a capsule containing a powdered or granular formulation can be construed as being "in the form of" microtablets or micropellets.
    • Technical Questions: An evidentiary question for the court will be to determine the actual physical characteristics of the formulation described in Mylan's ANDA. The dispute may center on whether the internal contents of the accused capsules are structurally and functionally equivalent to the "microtablets or micropellets" described and claimed in the patent.

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...with a pharmaceutical preparation The complaint alleges Mylan's product is for the treatment of multiple sclerosis, and that Mylan will encourage and instruct this use through its product labeling, which must copy the FDA-approved label for Tecfidera® (Compl. ¶¶6, 40). ¶¶6, 40 col. 8:14-16
wherein the only active ingredient for the treatment of multiple sclerosis present...is dimethyl fumarate. The accused product is identified as containing "dimethyl fumarate" in 120 mg and 240 mg strengths, and the complaint makes no mention of any other active ingredients for treating MS (Compl. ¶20). ¶20 col. 8:16-21
  • Identified Points of Contention:
    • Scope Questions: Practitioners may focus on the interpretation of "only active ingredient." The analysis will question whether any excipients in Mylan's formulation could be argued to have a therapeutic effect on multiple sclerosis, which might allow Defendant to contend that dimethyl fumarate is not the "only" active ingredient.
    • Technical Questions: For allegations of induced infringement, a key question will be whether the instructions for use in the proposed label for Mylan's product direct users to perform all steps of the claimed method. Since the ANDA process requires the generic label to mirror the innovator's label, the content of the approved Tecfidera® label will be central evidence.

V. Key Claim Terms for Construction

"microtablets or micropellets" (’376 Patent, Claim 1)

  • Context and Importance: This term defines the physical form of the claimed pharmaceutical composition. The infringement analysis for the composition patents (’376 and ’393) will hinge on whether the formulation detailed in Mylan’s confidential ANDA submission falls within the scope of this term.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification describes these as small units, optionally filled into capsules, intended to achieve gradual release in the intestine to improve tolerance. A party may argue that any small, coated, particulate formulation designed for this purpose, regardless of manufacturing method, meets the term's plain and ordinary meaning (’376 Patent, col. 4:34-54). The patent also provides a size range, stating the mean diameter is "in the range from 300 to 2,000 µm" (’376 Patent, col. 3:49-52).
    • Evidence for a Narrower Interpretation: The specification provides a specific example of making "micro-tablets" by compressing a powder mixture into "convex tablets having a gross weight of 10.0 mg and a diameter of 2.0 mm" (’376 Patent, col. 4:30-33). A party may argue this implies "microtablets" are distinct from "micropellets" and require a specific manufacturing process (compression) and structure not found in other particulate forms like granules or extruded spheres.

"only active ingredient" (’999 Patent, Claim 1)

  • Context and Importance: This term is critical for the method of treatment claims (’999 and ’840), as it defines the invention as a monotherapy. If Mylan's formulation contains any other substance that qualifies as an "active ingredient" for treating multiple sclerosis, it would not infringe these claims.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: A defendant could argue that "active ingredient" should be interpreted broadly to include any substance in the formulation with a known pharmacological effect relevant to MS, even if it is primarily included as an excipient.
    • Evidence for a Narrower Interpretation: The specification consistently distinguishes between the "active ingredient" (dialkyl fumarates) and "customary carriers and excipients" (’376 Patent, col. 3:40-42). A plaintiff may argue that the term should be limited to substances designated as "active pharmaceutical ingredients" under FDA regulatory standards for the specific indication of treating multiple sclerosis.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges both induced and contributory infringement for the asserted method-of-use patents (’999, ’001, ’840, ’514). The factual basis for inducement is the allegation that Mylan's product labeling, which by law must copy the FDA-approved Tecfidera® label, will instruct and encourage physicians and patients to administer the drug in an infringing manner (Compl. ¶¶40, 55, 70, 98). The basis for contributory infringement includes the allegation that the product is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶41, 56, 71, 99).

Willful Infringement

  • The complaint does not contain a formal count for willful infringement. However, it alleges that Mylan has "actual knowledge" of each asserted patent based on its June 1, 2017 Notice Letter, sent prior to the filing of the lawsuit (Compl. ¶¶22, 36, 51, 66, 81, 94). These allegations of pre-suit knowledge could potentially support a future claim for enhanced damages. The prayer for relief also requests the court to declare the case "exceptional" under 35 U.S.C. § 285, which is a basis for seeking attorneys' fees (Compl. ¶31).

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

  • A core issue will be one of structural scope: Does the specific formulation detailed in Mylan’s confidential ANDA for its "delayed-release capsules" meet the definition of a "pharmaceutical preparation in the form of microtablets or micropellets," as required by the asserted composition claims? The case may turn on whether Mylan's chosen delivery mechanism is structurally and functionally distinct from the claimed invention.
  • A second central question will be one of induced infringement: Given that Mylan is legally required to adopt a label materially similar to that of Tecfidera®, will the instructions on its proposed label inevitably direct medical professionals and patients to practice the patented methods of treatment, including the administration of dimethyl fumarate as the "only active ingredient" at a specific dosage of "about 480 mg per day"?
  • The dispute may also raise questions of claim differentiation across the patent family. The court will need to analyze how the subtle but distinct claim limitations across the six asserted patents—covering compositions, methods of use with a sole active ingredient, methods involving metabolites, and specific dosage regimens—apply to a single accused product.