DCT
1:21-cv-02117
Biogen Inc v. MSN Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Biogen International GmbH (Switzerland)
- Defendant: MSN Laboratories Private Ltd. (India) and MSN Pharmaceuticals Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes; Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.
- Case Identification: 1:18-cv-00337, D. Del., 03/01/2018
- Venue Allegations: Venue is alleged to be proper in Delaware because Defendant MSN Pharmaceuticals Inc. is a Delaware corporation, and Defendant MSN Laboratories Private Ltd. is an Indian corporation that may be sued in any judicial district.
- Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the multiple sclerosis drug Tecfidera® constitutes an act of infringement of two patents covering pharmaceutical formulations and methods of use.
- Technical Context: The technology concerns oral pharmaceutical formulations of dialkyl fumarates, specifically dimethyl fumarate, for treating autoimmune diseases like multiple sclerosis.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 210460 and a subsequent notice letter to the Plaintiff. The complaint notes a prior lawsuit involving the same ANDA but asserting a different patent. The asserted patents are listed in the FDA's "Orange Book" for Tecfidera®. The patents-in-suit are subject to terminal disclaimers, which may limit their effective term.
Case Timeline
| Date | Event |
|---|---|
| 1998-11-19 | Priority Date for '376 and '999 Patents |
| 2003-01-21 | '376 Patent Issued |
| 2008-01-22 | '999 Patent Issued |
| 2013-03-27 | FDA Approved Biogen's Tecfidera® (NDA No. 204063) |
| 2017-06-05 | MSN sent "First Notice Letter" regarding ANDA and a separate patent |
| 2018-01-17 | MSN sent "Second Notice Letter" regarding ANDA, '376 & '999 Patents |
| 2018-03-01 | Complaint 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 challenge of treating autoimmune diseases and preventing organ transplant rejection, noting that conventional immunosuppressive agents can cause severe side effects, such as increased risk of infection and malignant diseases (’376 Patent, col. 2:56-63).
- The Patented Solution: The invention is a pharmaceutical preparation using dialkyl fumarates formulated into "micro-tablets or micro-pellets," which may be enterically coated and placed in capsules (’376 Patent, Abstract; col. 3:32-38). This specific formulation is intended to allow for a "positive modulation of the immune system" while improving gastrointestinal tolerance compared to conventional tablets by avoiding high local concentrations of the active ingredient in the intestine (’376 Patent, col. 3:42-48; col. 5:29-54).
- Technical Importance: The invention proposed a therapeutic alternative for serious immune-mediated conditions that could potentially offer a more favorable side-effect profile than established immunosuppressants like cyclosporine (’376 Patent, col. 2:36-55).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶45).
- Essential elements of Claim 1 include:
- A pharmaceutical preparation in the form of microtablets or micropellets
- comprising one or more dialkyl fumarates of a specific chemical formula
- and optionally suitable carriers and excipients
- 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: As a divisional of the application leading to the '376 patent, the '999 patent shares the same technical background, addressing the need for effective treatments for autoimmune diseases such as multiple sclerosis (’999 Patent, col. 4:54-61).
- The Patented Solution: This patent claims a specific method of treating multiple sclerosis by administering a pharmaceutical preparation where dimethyl fumarate is the "only active ingredient" (’999 Patent, col. 8:14-19). This narrows the invention from the broader class of dialkyl fumarates and diseases in the parent patent to a specific compound for a specific indication. The specification carries over the disclosure regarding the benefits of micro-tablet formulations for improving patient tolerance (’999 Patent, col. 6:28-54).
- Technical Importance: The patent provides targeted protection for the use of a single, specified compound (dimethyl fumarate) as a monotherapy for multiple sclerosis, a commercially significant neurological disease (’999 Patent, col. 8:14-19).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶59).
- Essential elements of Claim 1 include:
- A method of treating multiple sclerosis
- comprising treating a patient in need 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.
III. The Accused Instrumentality
Product Identification
Defendants' proposed generic "dimethyl fumarate delayed-release capsules" in 120 mg and 240 mg strengths, as described in ANDA No. 210460 (Compl. ¶41).
Functionality and Market Context
The product is a generic equivalent of Biogen's branded drug, Tecfidera®, and is intended for the treatment of relapsing forms of multiple sclerosis (Compl. ¶¶ 2, 10, 39). As an ANDA product, it is designed to be therapeutically equivalent to Tecfidera®, and its proposed labeling is expected to mirror the instructions for use from the brand-name drug's FDA-approved package insert (Compl. ¶61). The filing of the ANDA signals Defendants' intent to market a lower-cost alternative to Tecfidera® upon receiving FDA approval (Compl. ¶10).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
'376 Patent 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 product described in ANDA No. 210460 is alleged to be a pharmaceutical preparation that contains or is formulated as microtablets or micropellets. | ¶45 | col. 3:32-38 |
| ...comprising one or more dialkyl fumarates of the formula... | Defendants' product contains dimethyl fumarate, which is a species of dialkyl fumarate covered by the claimed chemical formula. | ¶41 | col. 3:15-28 |
| ...for use in ... the therapy of autoimmune diseases such as ... multiple sclerosis... | Defendants' ANDA seeks approval to market its product for the treatment of relapsing forms of multiple sclerosis, an autoimmune disease. | ¶¶10, 41 | col. 3:55-58 |
'999 Patent 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 in need of treatment for multiple sclerosis... | Defendants' proposed product label will allegedly instruct physicians and patients to administer the drug for the treatment of multiple sclerosis. | ¶¶59, 61 | col. 8:14-16 |
| ...with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis... | The proposed product is supplied in 120 mg and 240 mg dosage strengths, which are alleged to be effective amounts for treating multiple sclerosis. | ¶41 | col. 8:16-18 |
| ...wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate. | The ANDA product is alleged to contain dimethyl fumarate as the sole active ingredient for the treatment of multiple sclerosis. | ¶41 | col. 8:18-19 |
- Identified Points of Contention:
- Technical Questions: A primary factual question for the '376 patent is whether the specific formulation described in Defendants' confidential ANDA meets the "microtablets or micropellets" limitation. The complaint does not provide this technical detail, making it a central point for discovery and expert testimony.
- Scope Questions: For the '999 patent, a potential dispute could arise over the meaning of "only active ingredient." The analysis will question whether any excipients in the accused product could be characterized as having a therapeutic effect on multiple sclerosis, which might place the product outside the claim's scope.
V. Key Claim Terms for Construction
Term 1: "microtablets or micropellets" ('376 Patent, Claim 1)
- Context and Importance: This term defines the physical form of the claimed composition. Infringement of claim 1 of the '376 patent hinges on whether Defendants' ANDA product, contained within a capsule, utilizes this specific formulation. Practitioners may focus on this term because the patent emphasizes this form as key to improving gastrointestinal tolerance.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims do not recite a specific size or manufacturing process, which may support an interpretation covering a range of small, compacted drug particles intended for enteric release.
- Evidence for a Narrower Interpretation: The specification describes a "preferred embodiment" where the pellets or micro-tablets have a size "in the range from 300 to 2,000 µm" (’376 Patent, col. 3:49-52). Example 1 also describes making "convex tablets having a ... diameter of 2.0 mm" (’376 Patent, col. 5:31-32). This disclosure could be used to argue for a narrower construction limited to these specified characteristics.
Term 2: "only active ingredient for the treatment of multiple sclerosis" ('999 Patent, Claim 1)
- Context and Importance: This limitation is critical for defining the scope of the method claim. The infringement case for the '999 patent requires that Defendants' product contains no other substance that qualifies as an active ingredient for treating multiple sclerosis.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (Plaintiff's View): A party may argue that "active ingredient" should be given its standard regulatory meaning, referring to the pharmacologically active substance (dimethyl fumarate) and excluding pharmaceutically inert excipients. The specification consistently focuses on dialkyl fumarates as the sole therapeutic agent (’999 Patent, col. 3:5-14).
- Evidence for a Narrower Interpretation (Defendant's View): A party could argue that if any excipient in the formulation has a known, independent therapeutic effect on multiple sclerosis or its symptoms, the "only" requirement is not met. The patent itself does not provide a definition that would explicitly counter such an argument, leaving the term open to interpretation based on its plain and ordinary meaning in the art.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement of the method claims of the '999 patent. The basis for this allegation is that Defendants' proposed product label, by copying the FDA-approved package insert for Tecfidera®, will instruct physicians and patients to use the drug in a manner that directly practices the patented method (Compl. ¶61). Contributory infringement is also alleged, based on the assertion that the product is a material part of the invention, is not a staple article of commerce, and is knowingly sold for an infringing use (Compl. ¶62).
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it alleges that Defendants have "actual knowledge" of the patents-in-suit as of the date of their notice letter (Compl. ¶¶ 43, 57) and requests that the court declare the case "exceptional" under 35 U.S.C. § 285, which could permit an award of attorneys' fees (Compl. p. 13, ¶11).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of structural characterization: Does the formulation detailed in Defendants' confidential ANDA filing fall within the scope of the term "microtablets or micropellets" as used in the '376 patent, or does it employ a distinct drug delivery technology that avoids this limitation?
- A second key issue will be one of induced infringement: Will the instructions on Defendants' proposed product label be found to demonstrate the specific intent required to encourage physicians and patients to perform the patented method of treating multiple sclerosis with a preparation containing only dimethyl fumarate as the active ingredient, as claimed in the '999 patent?
- The case may also turn on a question of claim construction: How will the court construe the term "only active ingredient" in the '999 patent? The outcome will depend on whether the term is limited to FDA-designated active pharmaceutical ingredients or if it could be interpreted more broadly to include any component with a therapeutic effect on the claimed indication.