DCT
1:17-cv-00856
Biogen Intl GmbH v. TWi Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Biogen International GmbH (Switzerland) and Biogen MA Inc. (Massachusetts)
- Defendant: TWi Pharmaceuticals, Inc. (Taiwan) and TWi Pharmaceuticals USA, Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes; Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.
- Case Identification: 1:17-cv-00856, D. Del., 06/28/2017
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant TWi USA is incorporated in Delaware, and because Defendant TWi Pharmaceuticals purposefully directed activities at the district, including by filing an Abbreviated New Drug Application (ANDA) seeking to market products there.
- Core Dispute: Plaintiff alleges that Defendants’ filing of an ANDA to market generic dimethyl fumarate delayed-release capsules, a generic version of Plaintiff’s Tecfidera® product, infringes two patents covering methods of treating multiple sclerosis.
- Technical Context: The technology concerns pharmaceutical formulations and methods for treating multiple sclerosis (MS), a chronic autoimmune and neurodegenerative disease, using dimethyl fumarate as the active therapeutic agent.
- Key Procedural History: This is a Hatch-Waxman action initiated after Defendants filed ANDA No. 210382 with a Paragraph IV certification and sent a corresponding notice letter to Plaintiff on May 23, 2017. The '514' patent was the subject of an inter partes review (IPR2015-01993), which concluded with a certificate dated February 22, 2018, confirming the patentability of all challenged claims, including the asserted claim 1. The '999' patent includes a terminal disclaimer disclaiming any patent term that would extend beyond the expiration of several related patents.
Case Timeline
| Date | Event |
|---|---|
| 1998-11-19 | U.S. Patent No. 7,320,999 Priority Date |
| 2007-02-08 | U.S. Patent No. 8,399,514 Priority Date |
| 2008-01-22 | U.S. Patent No. 7,320,999 Issued |
| 2013-03-19 | U.S. Patent No. 8,399,514 Issued |
| 2013-03-27 | FDA Approval of Tecfidera® (NDA No. 204063) |
| 2015-09-28 | IPR Proceeding (IPR2015-01993) Filed Against '514 Patent |
| 2017-05-23 | Defendants Send Notice Letter to Plaintiff |
| 2017-06-28 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
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 describes the dangers associated with conventional immunosuppressive agents used to treat autoimmune diseases, including the weakening of the body's defenses against infection and an increased risk of malignant diseases (’999 Patent, col. 4:56-60).
- The Patented Solution: The invention proposes using certain dialkyl fumarates to treat autoimmune diseases like multiple sclerosis. The patent explains that compositions containing these compounds, such as dimethyl fumarate (DMF), "surprisingly permit a positive modulation of the immune system" (’999 Patent, col. 5:45-48). The invention is directed to methods of treatment using a pharmaceutical preparation where DMF is the sole active ingredient, distinguishing it from prior art that used combinations of fumaric acid derivatives (’999 Patent, col. 5:50-55; col. 8:14-20).
- Technical Importance: This approach offered a method for treating MS with a specific, single active ingredient, potentially avoiding the side effects and complexities of prior combination therapies.
Key Claims at a Glance
- The complaint asserts independent claim 1 and reserves the right to assert others (Compl. ¶41).
- Independent Claim 1:
- A method of treating multiple sclerosis comprising
- treating a patient in need of treatment for multiple sclerosis
- 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.
U.S. Patent No. 8,399,514, "Treatment for Multiple Sclerosis," Issued Mar. 19, 2013
The Invention Explained
- Problem Addressed: The patent identifies a gap in MS therapy, noting that while many drugs reduce inflammation, they often fail to stop the underlying disease progression, which involves axonal loss and neuronal death (’514 Patent, col. 1:40-47). This neuronal damage is linked to oxidative stress (’514 Patent, col. 1:62-64).
- The Patented Solution: The invention is based on the discovery that DMF and its metabolite, monomethyl fumarate (MMF), provide neuroprotection by activating the Nrf2 cellular pathway, an endogenous defense mechanism against oxidative stress (’514 Patent, col. 2:15-18, col. 4:60-65). The patent claims a method of treating MS by orally administering a specific daily dose—about 480 mg—of DMF or MMF to achieve this neuroprotective effect (’514 Patent, col. 28:58-67).
- Technical Importance: The invention provided a novel, neuroprotective mechanism of action for DMF in treating MS, linking the clinical benefit to the activation of the Nrf2 pathway at a specific, therapeutically effective oral dose.
Key Claims at a Glance
- The complaint asserts independent claim 1 and reserves the right to assert others (Compl. ¶56).
- Independent Claim 1:
- A method of treating a subject in need of treatment for multiple sclerosis comprising
- orally administering to the subject in need thereof 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 of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.
III. The Accused Instrumentality
Product Identification
The subject of the litigation is Defendants' ANDA No. 210382, which seeks FDA approval to market generic "dimethyl fumarate delayed-release capsules containing 120 mg and 240 mg of dimethyl fumarate" (Compl. ¶10, ¶38).
Functionality and Market Context
The product described in the ANDA is a generic equivalent of Biogen's Tecfidera®, a drug approved for treating relapsing forms of multiple sclerosis (Compl. ¶3, ¶36-37). The complaint alleges that upon approval, the ANDA product will be sold for this purpose, with a label that copies the FDA-approved Tecfidera® label, thereby instructing physicians and patients on its use (Compl. ¶44, ¶59). The product is intended to be a lower-cost competitor to the branded drug.
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
'999 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating multiple sclerosis... | The ANDA product is intended and labeled for the treatment of multiple sclerosis (Compl. ¶44). | ¶41, ¶43 | col. 8:14 |
| ...with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis... | The ANDA product is a pharmaceutical preparation containing 120 mg and 240 mg of dimethyl fumarate, dosages intended to be effective for treating MS (Compl. ¶38). | ¶38, ¶42 | col. 8:15-16 |
| ...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 be a generic dimethyl fumarate formulation whose sole active ingredient is dimethyl fumarate (Compl. ¶38). | ¶38, ¶41 | col. 8:17-20 |
'514 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering...a pharmaceutical composition... | The ANDA product is a delayed-release capsule intended for oral administration to treat MS (Compl. ¶38, ¶59). | ¶38, ¶56 | col. 28:58-62 |
| ...consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate...and (b) one or more...excipients... | The ANDA product is alleged to contain a therapeutically effective amount of dimethyl fumarate and otherwise standard pharmaceutical excipients (Compl. ¶38, ¶60). | ¶38, ¶56 | col. 28:60-64 |
| ...wherein the therapeutically effective amount...is about 480 mg per day. | The complaint alleges infringement of this claim, which implies the ANDA product's labeling will instruct a daily dosage of about 480 mg (e.g., 240 mg twice daily), consistent with the approved Tecfidera® regimen. | ¶56, ¶59 | col. 28:64-67 |
- Identified Points of Contention:
- Scope Questions: For the ’514 Patent, the scope of "consisting essentially of" raises the question of whether any unlisted excipients in Defendants' formulation materially alter the basic and novel properties of the invention—namely, the neuroprotective effect attributed to the Nrf2 pathway activation.
- Technical Questions: A central question for the '514 patent is whether the proposed label for the ANDA product will, in fact, direct administration of "about 480 mg per day." Given the requirement for a generic label to mirror the branded label, this appears to be a direct factual inquiry.
V. Key Claim Terms for Construction
The Term: "only active ingredient" (’999 Patent, Claim 1)
- Context and Importance: This term strictly defines the composition. The infringement analysis depends on whether Defendants' ANDA product contains any other substance that could be characterized as an "active ingredient" for treating MS.
- Evidence for a Broader Interpretation: A party might argue the specification’s mention of using fumarates "alone or as a mixture of several compounds" suggests the "single agent" aspect was not the sole focus of the invention, but this is a weak argument against the plain language of the claim (’999 Patent, col. 5:40-41).
- Evidence for a Narrower Interpretation: The plain meaning of "only" provides the strongest evidence for a narrow construction. The patent distinguishes itself from prior art compositions that contained mixtures of fumaric acid derivatives, suggesting the limitation to a single active ingredient is a deliberate and critical element of the claim (’999 Patent, col. 5:50-55).
The Term: "consisting essentially of" (’514 Patent, Claim 1)
- Context and Importance: The construction of this transitional phrase is critical. It permits the presence of unlisted ingredients (excipients) so long as they do not materially affect the "basic and novel properties" of the claimed invention. Practitioners may focus on this term because the parties will likely dispute what those properties are and whether any specific excipient in the accused product has a material effect.
- Evidence for a Broader Interpretation: The patentee may argue the "basic and novel properties" are narrowly defined as neuroprotection via Nrf2 activation at the claimed dose, meaning only unlisted ingredients that interfere with this specific mechanism are material.
- Evidence for a Narrower Interpretation: The defendant may argue that properties such as the formulation's release profile, bioavailability, or side-effect profile are also "basic and novel," and that certain excipients in their product materially affect these properties, thereby placing the product outside the claim's scope.
The Term: "about 480 mg per day" (’514 Patent, Claim 1)
- Context and Importance: This dosage limitation is a core element of the infringement case. The meaning of "about" will determine the range of permissible daily doses that fall within the claim's scope.
- Evidence for a Broader Interpretation: The use of the word "about" inherently provides for some flexibility around the specific 480 mg value. The patentee may point to this term to argue that dosages reasonably close to 480 mg/day are covered.
- Evidence for a Narrower Interpretation: A defendant may argue that the scope of "about" must be interpreted in light of the specification and prosecution history. If the patentee distinguished prior art based on specific dosages, a court may narrow the term's scope to what is numerically very close to 480 mg.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement theory is predicated on Defendants' legal requirement to copy the FDA-approved Tecfidera® label for their generic product. This label allegedly instructs physicians and patients to administer the drug in a manner that directly infringes the asserted claims (Compl. ¶44, ¶59). Contributory infringement is alleged on the basis that the dimethyl fumarate capsules are not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶45, ¶60).
- Willful Infringement: The willfulness claim is based on Defendants' alleged pre-suit knowledge of the patents-in-suit, evidenced by the Notice Letter sent to Biogen on May 23, 2017 (Compl. ¶40, ¶55).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of validity: Can Defendants prove by clear and convincing evidence that the asserted claims are invalid for obviousness or lack of written description, particularly for the ’514 patent, which has already survived an IPR challenge on similar grounds?
- A key question of claim scope will be the interpretation of "consisting essentially of" in the ’514 patent. The outcome will depend on how the court defines the "basic and novel properties" of the invention and whether any unlisted components in the accused generic formulation are found to materially affect those properties.
- A dispositive evidentiary question will be one of infringement: Does the proposed drug label in Defendants' ANDA instruct a dosing regimen that falls within the scope of "about 480 mg per day" as required by claim 1 of the '514 patent?