DCT
1:18-cv-00350
Biogen Inc v. Impax Laboratories Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Biogen International GmbH (Switzerland)
- Defendant: Impax Laboratories, Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes
- Case Identification: 1:18-cv-00350, D. Del., 03/05/2018
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Impax is a Delaware corporation.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of dimethyl fumarate constitutes infringement of patents covering pharmaceutical formulations and methods for treating multiple sclerosis.
- Technical Context: The technology relates to pharmaceutical compositions of dialkyl fumarates, specifically formulated as micro-tablets or micro-pellets, used for treating autoimmune diseases such as multiple sclerosis.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a notice letter from Impax regarding its ANDA filing for a generic version of Biogen's drug, Tecfidera®. The complaint notes a prior, separate lawsuit involving the same ANDA but a different patent (U.S. Patent No. 8,399,514). This current case concerns two different patents and was prompted by a second notice letter from Impax. Both patents-in-suit are subject to terminal disclaimers filed in December 2017, which may affect their enforceable term.
Case Timeline
| Date | Event |
|---|---|
| 1998-11-19 | Priority Date for ’376 and ’999 Patents |
| 2003-01-21 | U.S. Patent No. 6,509,376 Issued |
| 2008-01-22 | U.S. Patent No. 7,320,999 Issued |
| 2013-03-27 | FDA Approved NDA No. 204063 (Tecfidera®) |
| 2017-06-05 | Impax sends First Notice Letter regarding '514 Patent |
| 2017-06-26 | Biogen files "First Suit" against Impax over '514 Patent |
| 2018-01-22 | Impax sends Second Notice Letter regarding '376 & '999 Patents |
| 2018-03-05 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,509,376, “Utilization of Dialkyfumarates,” issued Jan. 21, 2003
The Invention Explained
- Problem Addressed: The patent describes the challenge of treating autoimmune diseases and preventing transplant rejection. It notes that conventional immunosuppressive therapies carry significant risks, including weakening the body’s defenses against infection and increasing the risk of malignant diseases (’376 Patent, col. 2:56-59). Furthermore, prior oral formulations of fumaric acid derivatives were associated with severe side effects and high toxicity, limiting their therapeutic use (’376 Patent, col. 3:25-31).
- The Patented Solution: The invention claims a pharmaceutical preparation of dialkyl fumarates formulated as "micro-tablets or micropellets," which may be enteric-coated and placed in capsules (’376 Patent, Claim 1; col. 5:42-55). This formulation is designed to improve tolerance by releasing the active ingredient in smaller dosages within the intestine, thereby avoiding the high local concentrations that cause gastrointestinal irritation and other side effects associated with conventional tablets (’376 Patent, col. 5:30-55).
- Technical Importance: This formulation technology provided a potential solution to the dose-limiting side effects that had hampered the use of fumarates, enabling the delivery of therapeutically effective amounts of the drug for chronic autoimmune conditions.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶34).
- Independent Claim 1 requires:
- A pharmaceutical preparation in the form of "microtablets or micropellets."
- Comprising one or more dialkyl fumarates (such as dimethyl fumarate).
- For use in treating specified autoimmune diseases, including multiple sclerosis.
U.S. Patent No. 7,320,999, “Dimethyl Fumarate for the Treatment of Multiple Sclerosis,” issued Jan. 22, 2008
The Invention Explained
- Problem Addressed: The patent, which shares a specification with the ’376 Patent, addresses the need for effective treatments for multiple sclerosis that do not carry the significant disadvantages of general immunosuppression, such as increased risk of infection and malignancy (’999 Patent, col. 2:56-64).
- The Patented Solution: The invention is a specific method of treatment, not a composition. It claims a method for treating multiple sclerosis by administering a pharmaceutical preparation where dimethyl fumarate is the "only active ingredient" (’999 Patent, Claim 1). This narrows the focus from a class of compounds and diseases to a single compound for a single indication. The underlying benefit of the formulation technology described in the specification is improved patient tolerance (’999 Patent, col. 5:48-55).
- Technical Importance: The invention carves out a specific therapeutic use for dimethyl fumarate as a monotherapy for multiple sclerosis, providing a basis for patent protection tied directly to the clinical application of the drug.
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶48).
- Independent Claim 1 requires:
- A method of treating multiple sclerosis.
- Comprising treating a patient with an effective amount of a pharmaceutical preparation.
- Wherein the "only active ingredient" in the preparation is dimethyl fumarate.
III. The Accused Instrumentality
- Product Identification: Defendant Impax's proposed generic "dimethyl fumarate delayed-release capsules" in 120 mg and 240 mg strengths, as described in its Abbreviated New Drug Application (ANDA) No. 210286 (Compl. ¶31).
- Functionality and Market Context: The accused product is a generic version of Plaintiff's branded drug, Tecfidera®, which is approved and marketed for the treatment of relapsing forms of multiple sclerosis (Compl. ¶¶ 2, 30). The filing of the ANDA is a statutory act of infringement under 35 U.S.C. § 271(e)(2) that allows for the resolution of patent disputes before the generic product enters the market (Compl. ¶5).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint. The complaint alleges infringement "either literally or under the doctrine of equivalents" but does not contain a claim chart or specific technical details about the accused product's formulation beyond its identity as a dimethyl fumarate capsule (Compl. ¶¶ 34, 48).
'376 Patent 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 Defendant's generic "dimethyl fumarate delayed-release capsules" will infringe this claim, but does not specify whether the capsules contain microtablets, micropellets, or another formulation. | ¶31, ¶34 | col. 8:8-10 |
| comprising one or more dialkyl fumarates of the formula... | The ANDA product contains dimethyl fumarate, which is a dialkyl fumarate species covered by the claimed formula. | ¶31 | col. 3:25-28 |
| for use in...the therapy of autoimmune diseases such as...multiple sclerosis... | The accused product is a generic version of Tecfidera®, a drug indicated for the treatment of multiple sclerosis. | ¶29, ¶30 | col. 8:20-27 |
- Identified Points of Contention:
- Technical Question: A central factual question for discovery will be the physical form of the drug inside Impax’s "delayed-release capsules." The complaint does not allege that the capsules contain "microtablets or micropellets." The case may therefore turn on whether the accused formulation is an equivalent to the claimed form.
'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... | The complaint alleges Impax will induce infringement by physicians and patients, who will follow the instructions on the proposed product label to administer the drug for the treatment of multiple sclerosis. | ¶50, ¶51 | col. 8:14-18 |
| with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis... | Impax’s ANDA seeks approval for specific dosages (120 mg and 240 mg) intended to be effective for treating multiple sclerosis. | ¶31 | col. 8:15-18 |
| wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate. | The complaint alleges the ANDA product is "dimethyl fumarate delayed-release capsules," which suggests dimethyl fumarate is the sole active ingredient. Impax is required by regulation to copy the label of the reference drug, which is a monotherapy. | ¶31, ¶51 | col. 8:18-21 |
- Identified Points of Contention:
- Scope Question: Does the term "only active ingredient" preclude the presence of excipients that may have some minor pharmacological effect? The infringement analysis will depend on the definition of "active ingredient" as understood by a person of ordinary skill in the pharmaceutical arts.
V. Key Claim Terms for Construction
For the ’376 Patent
- The Term: "microtablets or micropellets"
- Context and Importance: This term is the central structural limitation of the asserted composition claim. As the complaint does not describe the physical structure of the accused generic product, the construction of this term will be critical in determining literal infringement. Practitioners may focus on this term because the dispute may hinge on whether Impax's formulation, whatever its form, falls within the scope of this definition.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not provide a formal definition, which could support an argument that the term should be given its plain and ordinary meaning, potentially covering a range of small, compacted drug particles.
- Evidence for a Narrower Interpretation: The specification provides specific examples, such as "convex tablets having a...diameter of 2.0 mm" (’376 Patent, col. 6:32-33) and pellets with a mean diameter in the range of "300 to 2,000 µm" (’376 Patent, col. 4:50-52). A party could argue these examples limit the term to discrete, manufactured units within a specific size range, as opposed to less defined granules or powders.
For the ’999 Patent
- The Term: "only active ingredient"
- Context and Importance: This limitation defines the claimed method as a monotherapy. The infringement analysis for the ’999 patent will turn on whether any other substance in Impax's formulation constitutes an "active ingredient."
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (of what constitutes an "active ingredient"): A party seeking to avoid infringement might argue that certain excipients that are not inert and have some pharmacological effect could be considered additional "active ingredients," even if they are not the primary therapeutic agent.
- Evidence for a Narrower Interpretation (of what constitutes an "active ingredient"): The patent consistently distinguishes between the "active ingredient" (dialkyl fumarates) and "customary carriers and excipients" (’999 Patent, col. 4:40-42). This suggests the term "active ingredient" refers specifically to the compound intended to provide the primary therapeutic effect for the indicated disease, not other components of the formulation.
VI. Other Allegations
- Indirect Infringement: For the '999 method patent, the complaint alleges both induced and contributory infringement.
- Inducement: It is alleged that Impax will induce infringement by physicians and patients by providing a product with a label that instructs users to take the drug for the treatment of multiple sclerosis (Compl. ¶51). The legal requirement that a generic label copy the branded drug's label may support the allegation of intent.
- Contributory Infringement: It is alleged that Impax's capsules are a material part of the invention, are not a staple article of commerce suitable for substantial non-infringing use, and are sold with knowledge of their use in an infringing manner (Compl. ¶52).
- Willful Infringement: The complaint does not explicitly allege "willful infringement" or seek enhanced damages. However, it does allege that Impax has "actual knowledge" of the patents-in-suit via its notice letter (Compl. ¶¶ 33, 47) and requests that the court declare the case "exceptional" under 35 U.S.C. § 285, which provides for an award of attorney fees (Prayer for Relief ¶11).
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this case will likely depend on the answers to a few central questions that blend claim construction with factual evidence from the confidential ANDA filing.
- A core issue will be one of physical form: Can the formulation inside Impax’s "delayed-release capsules" be properly characterized as "microtablets or micropellets" under the court’s construction of that term in the ’376 patent, either literally or as a legal equivalent?
- A second key question will be one of compositional scope: Does Impax’s proposed generic product contain any substance, other than dimethyl fumarate, that qualifies as an "active ingredient" under the proper construction of that term in the ’999 patent?
- Finally, for the method claims of the '999 patent, a dispositive question will be one of inducement: Does the proposed label for Impax's generic product provide sufficient instruction and encouragement to physicians and patients to practice the claimed method of treating multiple sclerosis, thereby establishing the requisite intent for induced infringement?