DCT

1:23-cv-00732

Biogen Inc. v. Zydus Worldwide DMCC

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:23-cv-00732, D. Del., 07/06/2023
  • Venue Allegations: The complaint alleges venue is proper for the foreign defendants, Zydus Worldwide and Zydus Lifesciences, in any judicial district. Venue for Zydus USA is based on its subjection to personal jurisdiction in Delaware and its alleged prior consent to venue in the district in numerous other patent litigations.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the multiple sclerosis drug Vumerity® constitutes an act of infringement of three patents covering the drug's active compound, a method of its use, and a specific crystalline form.
  • Technical Context: The technology concerns pharmaceutical prodrugs of fumarates, specifically diroximel fumarate, designed to treat neurodegenerative diseases like multiple sclerosis with improved tolerability over earlier therapies.
  • Key Procedural History: This Hatch-Waxman action was triggered by Defendants' submission of ANDA No. 218596 with a Paragraph IV certification, asserting that Plaintiffs’ patents are invalid, unenforceable, or will not be infringed. Plaintiffs received a notice letter regarding the ANDA filing on May 25, 2023, and filed this complaint within the statutory 45-day period.

Case Timeline

Date Event
2013-03-14 Earliest Priority Date for ’281, ’558, and ’733 Patents
2014-03-11 U.S. Patent No. 8,669,281 Issues
2015-07-28 U.S. Patent No. 9,090,558 Issues
2018-09-25 U.S. Patent No. 10,080,733 Issues
2023-05-25 Zydus sends Notice Letter regarding ANDA filing to Plaintiffs
2023-07-06 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,669,281 - “Prodrugs of Fumarates and Their Use in Treating Various Diseases”

  • Issued: March 11, 2014

The Invention Explained

  • Problem Addressed: The patent background describes existing fumaric acid ester (FAE) therapies, such as dimethyl fumarate (DMF), as being effective for conditions like psoriasis and multiple sclerosis (MS) but associated with significant drawbacks, including flushing and gastrointestinal side effects that affect 70-90% of patients, and a frequent dosing schedule that can hinder patient compliance (’733 Patent, col. 3:9-17).
  • The Patented Solution: The invention provides novel prodrugs of monomethyl fumarate (MMF), which is the main bioactive metabolite of DMF (’733 Patent, col. 2:21-26). These new compounds are designed to be converted in vivo to MMF, thereby retaining the therapeutic advantages of DMF while offering improved properties, such as potentially reduced side effects or a more favorable dosing profile (’733 Patent, col. 4:8-13). The ’281 patent specifically claims one such novel compound, diroximel fumarate.
  • Technical Importance: The invention represents a therapeutic strategy to improve patient tolerability and adherence by creating a new molecular entity that delivers a known active metabolite, potentially overcoming the limitations of prior-generation drugs in the same class (’733 Patent, col. 3:36-44).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶39).
  • Claim 1 recites the following essential elements:
    • A compound having a specific chemical formula (diroximel fumarate).
    • Or a pharmaceutically acceptable salt thereof.
  • The complaint alleges infringement of "one or more claims," including at least claim 1, thereby reserving the right to assert other claims (Compl. ¶40).

U.S. Patent No. 9,090,558 - “Prodrugs of Fumarates and Their Use in Treating Various Diseases”

  • Issued: July 28, 2015

The Invention Explained

  • Problem Addressed: As with the ’281 Patent, this patent addresses the need for improved fumarate-based therapies for neurological diseases like MS that overcome the side effects and dosing challenges associated with dimethyl fumarate (’733 Patent, col. 3:9-17).
  • The Patented Solution: The patent claims a method of using the specific compound, diroximel fumarate, to treat multiple sclerosis. Instead of claiming the compound itself, this patent protects the act of administering the compound for a specific therapeutic purpose, thereby providing a different layer of intellectual property protection (’733 Patent, col. 4:62-65).
  • Technical Importance: This patent directly protects the commercial application of diroximel fumarate as a treatment for MS, linking the novel compound to a specific, high-value medical indication.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶52).
  • Claim 1 recites the following essential elements:
    • A method of treating multiple sclerosis in a subject in need thereof.
    • Comprising administering to the subject a therapeutically effective amount of a compound having the formula for diroximel fumarate.
    • Or a pharmaceutically acceptable salt thereof.
  • The complaint alleges infringement of "one or more claims," including at least claim 1, thereby reserving the right to assert other claims (Compl. ¶53).

U.S. Patent No. 10,080,733 - “Prodrugs of Fumarates and Their Use in Treating Various Diseases”

  • Issued: September 25, 2018

Technology Synopsis

  • This patent claims a specific solid-state form—a crystalline polymorph—of the diroximel fumarate compound claimed in the ’281 patent (’733 Patent, col. 1:21-26, Claim 1). Pharmaceutical compounds can often exist in multiple crystalline forms, each with different physical properties affecting stability, dissolution, and manufacturability; this patent protects one such specific form identified by its characteristic X-ray powder diffraction (XRPD) pattern (’733 Patent, Claim 1).

Asserted Claims

  • The complaint asserts independent claim 1 (Compl. ¶66).

Accused Features

  • The complaint alleges that the active pharmaceutical ingredient in Zydus's ANDA Product is or contains the claimed crystalline form of diroximel fumarate, as defined by its specific XRPD peaks (Compl. ¶65-66).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Zydus's ANDA Product," identified as a generic version of Vumerity® (diroximel fumarate) in 231 mg delayed-release capsules, for which Zydus submitted ANDA No. 218596 to the FDA (Compl. ¶1).

Functionality and Market Context

  • The product is a drug intended for the treatment of relapsing forms of multiple sclerosis (MS) (Compl. ¶2). The complaint alleges that upon FDA approval, the product will be marketed in the United States as a direct competitor to Plaintiffs' Vumerity® product (Compl. ¶2, ¶9). The chemical structure depicted in the complaint for the active compound is that of diroximel fumarate (Compl. ¶38).

IV. Analysis of Infringement Allegations

’281 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound having the formula: [structure] or a pharmaceutically acceptable salt thereof. The active ingredient in Zydus's ANDA Product is alleged to be diroximel fumarate, the compound having the specific chemical formula recited in the claim. The chemical structure shown in the complaint illustrates this compound. ¶38, ¶39 col. 20:40

’558 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating multiple sclerosis in a subject in need thereof, Zydus’s proposed product labeling allegedly directs medical professionals and patients to use the ANDA product for the treatment of MS. ¶53 col. 4:62-65
comprising administering to the subject a therapeutically effective amount of a compound having the formula: [structure] or a pharmaceutically acceptable salt thereof. Zydus's ANDA Product contains the claimed compound, and its proposed labeling allegedly directs administration of a therapeutically effective amount for treating MS. The complaint provides the relevant chemical structure. ¶51, ¶53 col. 20:40

Identified Points of Contention

  • Scope Questions: For the ’558 patent, a potential dispute may arise over the scope of "treating multiple sclerosis." The parties could contest whether the specific instructions in Zydus’s proposed label constitute "treating" as the term is used and defined within the patent specification, which discusses various forms and stages of MS (’733 Patent, col. 2:37-52).
  • Technical Questions: For the ’281 patent, the infringement analysis raises a direct factual question: is the active pharmaceutical ingredient in Zydus’s ANDA Product the specific compound claimed? In ANDA litigation, this is often confirmed through chemical analysis. For the ’733 patent, the central technical question will be whether Zydus's product exhibits the five specific X-ray diffraction peaks required by claim 1, a determination that will likely rely on competing expert analyses.

V. Key Claim Terms for Construction

  • The Term: "treating multiple sclerosis" (from Claim 1 of the ’558 Patent)
  • Context and Importance: The definition of this term is critical for the induced infringement analysis of the ’558 patent. The infringement allegation rests on the assertion that Zydus’s proposed product label will instruct users to perform the claimed method. Practitioners may focus on this term because if Zydus’s label contains instructions for an indication that falls outside a narrowly construed definition of "treating multiple sclerosis," Zydus could argue it does not induce infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes MS broadly, listing four major clinical types: relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), primary progressive MS (PPMS), and progressive relapsing MS (PRMS) (’733 Patent, col. 2:37-52). This language could support a construction where "treating" covers any therapeutic intervention for any of these recognized forms of the disease.
    • Evidence for a Narrower Interpretation: The background section highlights a Phase IIb study of a related compound where the therapeutic effect was measured by a reduction in "gadolinium-enhancing brain lesions" (’733 Patent, col. 2:30-32). A defendant could potentially argue that "treating," in the context of the patent, requires achieving this or a similarly specific clinical outcome, rather than just general administration for the disease.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges active inducement of infringement for all three asserted patents. The basis for this allegation is that Zydus has knowledge of the patents, at least from their listing in the FDA's Orange Book, and that Zydus's proposed product labeling will instruct physicians and patients to use the ANDA product in an infringing manner (Compl. ¶46-47, ¶59-60, ¶73-74). Contributory infringement is also alleged for the ’558 and ’733 patents, based on the assertion that Zydus's product is especially made or adapted for infringing the method-of-use and crystalline form claims and is not a staple article of commerce with substantial noninfringing uses (Compl. ¶61, ¶75).

Willful Infringement

  • The complaint does not use the word "willful" but does request a declaration that the case is "exceptional" and an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. p. 14, ¶(e)). The allegations of knowledge of the patents via the Orange Book listing establish a basis for pre-suit knowledge, which could support a future claim for enhanced damages or a finding of an exceptional case (Compl. ¶46, ¶59, ¶73).

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

The resolution of this case will likely depend on the answers to several central questions before the court.

  • A primary issue will be one of patent validity: having filed a Paragraph IV certification, Zydus will bear the burden of proving by clear and convincing evidence that the asserted claims of the ’281, ’558, and ’733 patents are invalid, likely on grounds such as obviousness in light of prior art fumarate-based therapies or lack of adequate written description.
  • A key evidentiary question will be one of physical identity: does the active pharmaceutical ingredient in Zydus’s ANDA Product exist in the specific crystalline form defined by the five characteristic X-ray powder diffraction peaks recited in Claim 1 of the ’733 patent?
  • A third core issue will be one of induced infringement: does the language of Zydus's proposed product label, as submitted to the FDA, instruct, encourage, or otherwise lead medical professionals to prescribe, and patients to use, the generic product in a manner that directly infringes the method of "treating multiple sclerosis" as claimed in the ’558 patent?