DCT
1:17-cv-00857
Biogen Intl GmbH v. Macleods Pharmace
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Biogen International GmbH (Switzerland) and Biogen MA Inc. (Massachusetts)
- Defendant: Macleods Pharmaceuticals, Ltd. (India) and Macleods Pharma USA, Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes
- Case Identification: 1:17-cv-00857, D. Del., 06/28/2017
- Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant Macleods USA is incorporated in Delaware, and its co-defendant, an alien corporation, may be sued in any district. The complaint further alleges that the filing of an Abbreviated New Drug Application (ANDA) and the intent to market the generic product in Delaware constitute purposeful availment.
- 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 three patents related to pharmaceutical formulations and methods of using dimethyl fumarate.
- Technical Context: The technology concerns oral pharmaceutical dosage forms for dimethyl fumarate, a compound used to treat relapsing forms of multiple sclerosis, a significant autoimmune and neurological disease.
- Key Procedural History: The complaint notes that Macleods sent Biogen a Notice Letter dated June 2, 2017, pursuant to the Hatch-Waxman Act, certifying its ANDA filing and triggering this lawsuit. The '376 and '999 patents-in-suit contain terminal disclaimers, linking their expiration to other patents. U.S. Patent No. 8,399,514 survived an Inter Partes Review (IPR) proceeding (IPR2015-01993), with a certificate issuing on February 22, 2018 confirming the patentability of claims 1-20, a fact that may strengthen its presumption of validity.
Case Timeline
| Date | Event |
|---|---|
| 1998-11-19 | Priority Date for ’376 and ’999 Patents |
| 2003-01-21 | Issue Date for U.S. Patent No. 6,509,376 |
| 2007-02-08 | Priority Date for ’514 Patent |
| 2008-01-22 | Issue Date for U.S. Patent No. 7,320,999 |
| 2013-03-19 | Issue Date for U.S. Patent No. 8,399,514 |
| 2013-03-27 | FDA Approval for Tecfidera® (NDA No. 204063) |
| 2015-09-28 | Inter Partes Review Filed on ’514 Patent |
| 2017-06-02 | Macleods sends Notice Letter to Biogen |
| 2017-06-28 | Complaint Filing Date |
| 2018-02-22 | Inter Partes Review Certificate Issued for ’514 Patent |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,509,376 - "Utilization of Dialkyfumarates"
The Invention Explained
- Problem Addressed: The patent describes the challenge of treating autoimmune diseases and preventing transplant rejection. It notes that existing immunosuppressive therapies can have severe disadvantages, including weakening the body's defenses against infection and increasing the risk of malignant diseases (’376 Patent, col. 2:56-59). Furthermore, prior oral administration of fumaric acid derivatives was associated with high toxicity and severe side effects, particularly gastrointestinal irritation (’376 Patent, col. 3:20-29).
- The Patented Solution: The invention claims a pharmaceutical preparation of dialkyl fumarates formulated as "microtablets or micropellets" (’376 Patent, Abstract). This formulation is designed to allow for the controlled release of the active ingredient in the intestine. By distributing the drug in small, enteric-coated particles, the invention seeks to avoid the high local concentrations that cause gastrointestinal irritation, thereby improving the drug's tolerance and therapeutic utility (’376 Patent, col. 5:30-54).
- Technical Importance: This formulation technology provided a method for oral delivery of fumaric acid derivatives for systemic immune modulation while mitigating known gastrointestinal side effects that had previously limited their clinical use.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶42).
- Claim 1 Elements:
- A pharmaceutical preparation in the form of microtablets or micropellets.
- Comprising one or more dialkyl fumarates according to a specified chemical formula.
- Optionally including suitable carriers and excipients.
- For use in transplantation medicine or for the therapy of autoimmune diseases.
- The complaint does not explicitly reserve the right to assert dependent claims for the ’376 Patent.
U.S. Patent No. 7,320,999 - "Dimethyl Fumarate for the Treatment of Multiple Sclerosis"
The Invention Explained
- Problem Addressed: As a divisional of the application leading to the ’376 patent, the background addresses the same general problem: the need for effective and well-tolerated treatments for autoimmune diseases (’999 Patent, col. 2:25-40).
- The Patented Solution: This invention is a method for treating multiple sclerosis specifically. It claims the administration of a pharmaceutical preparation where dimethyl fumarate is the "only active ingredient" for treating MS (’999 Patent, col. 8:15-20). This narrows the focus from a broad class of compounds and formulations for general autoimmune conditions to a specific monotherapy for a specific disease.
- Technical Importance: The patent claims the specific indication of dimethyl fumarate as a sole active agent for treating multiple sclerosis, directly tying the compound to a key neurological disease.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶56).
- Claim 1 Elements:
- 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 the preparation is dimethyl fumarate.
- The complaint does not explicitly reserve the right to assert dependent claims for the ’999 Patent.
U.S. Patent No. 8,399,514 - "Treatment for Multiple Sclerosis"
- Technology Synopsis: This patent claims a method for treating multiple sclerosis by orally administering a specific daily dose of a pharmaceutical composition. The key inventive concept is the dosage regimen of "about 480 mg per day" of dimethyl fumarate, monomethyl fumarate, or a combination thereof, to achieve a therapeutic effect (’514 Patent, Abstract; col. 28:59-65).
- Asserted Claims: The complaint asserts at least independent claim 1 (Compl. ¶71).
- Accused Features: Plaintiff alleges that Defendant’s proposed generic product, available in 120 mg and 240 mg capsules, is intended to be prescribed and used in a manner that directly practices the claimed 480 mg per day dosing method (Compl. ¶¶39, 72-73).
III. The Accused Instrumentality
Product Identification
- Defendant’s proposed generic "dimethyl fumarate delayed-release capsules containing 120 mg and 240 mg of dimethyl fumarate" (Compl. ¶39).
Functionality and Market Context
- The accused product is a generic drug for which Defendant filed ANDA No. 210377, seeking FDA approval to market it as a bioequivalent substitute for Plaintiff's Tecfidera® product (Compl. ¶¶10, 39). The product is intended for oral administration for the treatment of relapsing forms of multiple sclerosis (Compl. ¶3). The filing of the ANDA itself, which seeks approval for this use prior to the expiration of the patents-in-suit, constitutes the act of infringement alleged in the complaint under 35 U.S.C. § 271(e)(2) (Compl. ¶43).
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 |
|---|---|---|---|
| Pharmaceutical preparation in the form of microtablets or micropellets | The complaint alleges that the product described in ANDA No. 210377 would, if marketed, meet this physical formulation requirement. | ¶43 | col. 8:9-10 |
| comprising one or more dialkyl fumarates of the formula... | The accused product is identified as containing dimethyl fumarate, which is a species of dialkyl fumarate covered by the claimed formula. | ¶39 | col. 4:25-27 |
| for use in... therapy of autoimmune diseases such as... multiple sclerosis... | Defendant’s ANDA seeks approval for the product to be used for the treatment of relapsing forms of multiple sclerosis, an autoimmune disease explicitly mentioned in the patent. | ¶3, ¶39 | col. 8:23-25 |
- Identified Points of Contention:
- Scope Questions: A central question may be whether the term "microtablets or micropellets" reads on the specific physical formulation of the generic drug described in Defendant’s ANDA.
- Technical Questions: The complaint does not provide specific factual allegations about the physical structure of the proposed generic product. A key evidentiary issue will be what Defendant’s ANDA discloses about the product's formulation and whether that disclosure supports a finding that it meets the structural limitations of the claim.
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... | Defendant’s ANDA seeks approval to market its product for the treatment of multiple sclerosis, which would induce physicians and patients to perform the claimed method. | ¶39, ¶59 | col. 8:15-16 |
| with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis | The proposed generic product is intended to be a therapeutically effective treatment for multiple sclerosis. | ¶39 | col. 8:17-18 |
| wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate. | The accused product is identified as "dimethyl fumarate delayed-release capsules," which suggests dimethyl fumarate is the sole active ingredient for treating MS. | ¶39 | col. 8:18-20 |
- Identified Points of Contention:
- Scope Questions: The interpretation of "only active ingredient" will be critical. The analysis will turn on whether any other components in the accused formulation could be considered "active" for the treatment of MS.
- Technical Questions: The infringement analysis will depend on the complete formulation disclosed in the ANDA. What evidence does the complaint provide that no other substance in the proposed generic product contributes to the therapeutic effect for MS?
V. Key Claim Terms for Construction
For the ’376 Patent:
- The Term: "microtablets or micropellets"
- Context and Importance: This term defines the physical structure of the claimed pharmaceutical preparation. Infringement of claim 1 of the ’376 patent hinges on whether the accused product embodies this specific form. Practitioners may focus on this term because it is the primary structural limitation that appears to distinguish the claimed invention from conventional oral dosage forms.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes various methods of production, including compressing a powder mixture into convex tablets with a 2.0 mm diameter or coating nonpareilles pellets with the active ingredient (’376 Patent, col. 6:29-33; col. 7:12-24). A party may argue these are merely exemplary and the term should encompass any small, particulate dosage form intended for filling into a capsule.
- Evidence for a Narrower Interpretation: The specification links the micro-tablet form to the technical advantage of avoiding high local concentrations of the active ingredient and consequent gastrointestinal irritation (’376 Patent, col. 5:30-54). Additionally, a preferred embodiment specifies a size or mean diameter in the range of 300 to 2,000 µm (’376 Patent, col. 4:49-52). A party may argue the term should be limited to structures that achieve this functional benefit or fall within this size range.
For the ’999 Patent:
- The Term: "only active ingredient"
- Context and Importance: This term is dispositive for infringement of the asserted method claim. If the accused product contains any other substance considered an "active ingredient" for treating multiple sclerosis, it would fall outside the claim's scope.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (of what is not an active ingredient): The patent's examples list numerous common pharmaceutical excipients, such as starch derivatives, cellulose, talcum, and Mg stearate, distinguishing them from the "active ingredient" (’999 Patent, col. 6:19-31). A party could argue that "active ingredient" refers only to the primary therapeutic agent recognized for treating the disease, and that standard excipients are, by definition, not active.
- Evidence for a Narrower Interpretation (of what is an active ingredient): The term is not explicitly defined in the patent. A party could argue that any component of the formulation that provides a therapeutic benefit for MS, even if secondary to dimethyl fumarate, could be construed as an "active ingredient," thereby avoiding infringement.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for the asserted method patents (’999 and ’514 Patents). Inducement is alleged based on Defendant’s intent to have physicians and patients use the product according to its label, which will be a copy of the FDA-approved Tecfidera® label and will instruct the infringing use (Compl. ¶¶59, 74). Contributory infringement is alleged on the basis that the product is a material part of the invention, is not a staple article of commerce suitable for substantial non-infringing use, and is known by Defendant to be especially made for an infringing use (Compl. ¶¶60, 75).
- Willful Infringement: The complaint does not explicitly plead "willful infringement." However, it alleges that Defendant has had "actual knowledge" of each of the patents-in-suit since at least the date of its Notice Letter on June 2, 2017, which may form the basis for a future claim of willfulness based on post-filing conduct (Compl. ¶¶41, 55, 70).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of structural scope: can the term "microtablets or micropellets" in the ’376 patent, which is linked in the specification to avoiding gastrointestinal irritation, be construed to cover the specific physical formulation of Defendant’s proposed generic drug as disclosed in its ANDA?
- A key compositional question will be one of therapeutic exclusivity: does the accused product’s formulation contain only dimethyl fumarate as the "only active ingredient" for treating multiple sclerosis as required by the ’999 patent, or could other excipients in the proposed generic be construed as contributing to the therapeutic effect?
- A central strategic question will be the impact of prior administrative adjudication: how will the confirmed patentability of the ’514 patent’s dosage claims, following a successful defense in an Inter Partes Review, influence Defendant’s litigation strategy regarding validity challenges and potentially shift the case’s focus toward non-infringement arguments or the other asserted patents?