DCT

8:17-cv-01133

Biogen Intl GmbH v. Stason Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:

  • Case Identification: 8:17-cv-01133, C.D. Cal., 06/30/2017

  • Venue Allegations: Venue is alleged to be proper in the Central District of California because Defendant Stason Pharmaceuticals, Inc. is incorporated in California.

  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) for generic dimethyl fumarate delayed-release capsules infringes six patents related to pharmaceutical compositions and methods of treating multiple sclerosis.

  • Technical Context: The patents relate to pharmaceutical formulations of dialkyl fumarates, primarily dimethyl fumarate, and methods for using them to treat autoimmune diseases, particularly the neurological condition multiple sclerosis.

  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Notice Letter dated May 31, 2017, informing them that Defendants had filed an ANDA with a Paragraph IV certification seeking FDA approval to market a generic version of Plaintiffs' Tecfidera® product prior to the expiration of the patents-in-suit.

Case Timeline

Date Event
1998-11-19 Priority Date for ’376, ’999, ’001, ’840, and ’393 Patents
2003-01-21 U.S. Patent No. 6,509,376 Issues
2007-02-08 Priority Date for ’514 Patent
2008-01-22 U.S. Patent No. 7,320,999 Issues
2009-11-17 U.S. Patent No. 7,619,001 Issues
2010-09-28 U.S. Patent No. 7,803,840 Issues
2013-03-19 U.S. Patent No. 8,399,514 Issues
2013-03-27 FDA approves NDA for Tecfidera®
2014-06-24 U.S. Patent No. 8,759,393 Issues
2017-05-31 Date of Defendants' ANDA Notice Letter to Plaintiff
2017-06-30 Complaint Filed

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

U.S. Patent No. 6,509,376 - "Utilization of Dialkyfumarates"

  • Patent Identification: U.S. Patent No. 6509376, "Utilization of Dialkyfumarates," issued January 21, 2003. (Compl. ¶21).

The Invention Explained

  • Problem Addressed: The patent addresses the significant side effects of conventional immunosuppressive agents used in transplantation medicine and for treating autoimmune diseases, noting that these agents weaken the body's defenses against infection and increase the risk of malignant diseases. (Compl. Ex. A, ’376 Patent, col. 2:56-62).
  • The Patented Solution: The invention proposes the use of certain dialkyl fumarates for preparing pharmaceutical compositions, particularly in the form of micro-tablets or pellets, to treat autoimmune diseases and transplant rejections. (Compl. Ex. A, ’376 Patent, Abstract). This formulation is intended to provide a "positive modulation of the immune system" with an improved safety profile compared to existing therapies. (Compl. Ex. A, ’376 Patent, col. 3:46-54).
  • Technical Importance: This approach sought to provide a therapeutic option for serious immune-related conditions that could potentially avoid the severe side effects associated with established treatments like cyclosporine. (Compl. Ex. A, ’376 Patent, col. 5:25-30).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶¶31, 32, 34).
  • Claim 1 of the ’376 Patent requires:
    • A pharmaceutical preparation in the form of microtablets or micropellets.
    • Comprising one or more dialkyl fumarates of a specified chemical formula.
    • Optionally comprising suitable carriers and excipients.
    • For use in transplantation medicine or for the therapy of specified autoimmune diseases, including multiple sclerosis. (Compl. Ex. A, ’376 Patent, col. 8:8-27).
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 7,320,999 - "Dimethyl Fumarate for the Treatment of Multiple Sclerosis"

  • Patent Identification: U.S. Patent No. 7320999, "Dimethyl Fumarate for the Treatment of Multiple Sclerosis," issued January 22, 2008. (Compl. ¶38).

The Invention Explained

  • Problem Addressed: As a divisional of the application leading to the ’376 patent, this patent addresses the same problem of finding safer and more effective treatments for autoimmune diseases, with a specific focus on multiple sclerosis. (Compl. Ex. B, ’999 Patent, col. 1:52-col. 2:50).
  • The Patented Solution: The invention claims a method of treating multiple sclerosis by administering a pharmaceutical preparation where dimethyl fumarate is the "only active ingredient" for the treatment. (Compl. Ex. B, ’999 Patent, Abstract; col. 8:15-22). This narrows the broad disclosures of the parent patent to a specific compound for a specific indication.
  • Technical Importance: The invention claims a targeted therapeutic method using a single specified active agent for multiple sclerosis, differentiating it from combination therapies or broader compositions for general autoimmune conditions. (Compl. Ex. B, ’999 Patent, col. 3:42-53).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1. (Compl. ¶¶45, 46, 47).
  • Claim 1 of the ’999 Patent requires:
    • 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 pharmaceutical preparation is dimethyl fumarate. (Compl. Ex. B, ’999 Patent, col. 8:15-22).
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 7,619,001 - "Utilization of Dialkylfumarates"

  • Patent Identification: U.S. Patent No. 7619001, "Utilization of Dialkylfumarates," issued November 17, 2009. (Compl. ¶53).
  • Technology Synopsis: This patent, related to the ’376 and ’999 patents, claims methods of treating multiple sclerosis by administering a pharmaceutical preparation comprising either dimethyl fumarate, methyl hydrogen fumarate, or a combination thereof. (Compl. Ex. C, ’001 Patent, Abstract; col. 8:28-34).
  • Asserted Claims: Independent claim 1 is asserted. (Compl. ¶¶60-62).
  • Accused Features: Defendants' ANDA product, a generic dimethyl fumarate capsule for treating multiple sclerosis, is accused of infringing. (Compl. ¶¶57, 60).

U.S. Patent No. 7,803,840 - "Utilization of Dialkylfumarates"

  • Patent Identification: U.S. Patent No. 7803840, "Utilization of Dialkylfumarates," issued September 28, 2010. (Compl. ¶68).
  • Technology Synopsis: This patent, also in the same family, claims methods for treating autoimmune diseases, including polyarthritis and multiple sclerosis, where the only active ingredient is dimethyl fumarate. (Compl. Ex. D, ’840 Patent, Abstract; col. 8:29-41).
  • Asserted Claims: Independent claim 1 is asserted. (Compl. ¶¶75-77).
  • Accused Features: Defendants' ANDA product, a generic dimethyl fumarate capsule for treating multiple sclerosis, is accused of infringing. (Compl. ¶¶72, 75).

U.S. Patent No. 8,759,393 - "Utilization of Dialkylfumarates"

  • Patent Identification: U.S. Patent No. 8759393, "Utilization of Dialkylfumarates," issued June 24, 2014. (Compl. ¶83).
  • Technology Synopsis: This patent claims pharmaceutical preparations in the form of microtablets comprising dimethyl fumarate as the active ingredient. The claims are directed to the composition itself, similar to the ’376 patent, but are more specific as to the identity of the fumarate. (Compl. Ex. E, ’393 Patent, Abstract; col. 8:19-22).
  • Asserted Claims: Independent claim 1 is asserted. (Compl. ¶¶90, 91).
  • Accused Features: Defendants' ANDA product for generic dimethyl fumarate capsules is accused of infringing. (Compl. ¶¶87, 90).

U.S. Patent No. 8,399,514 - "Treatment for Multiple Sclerosis"

  • Patent Identification: U.S. Patent No. 8399514, "Treatment for Multiple Sclerosis," issued March 19, 2013. (Compl. ¶96).
  • Technology Synopsis: This patent claims methods of treating multiple sclerosis by orally administering a specific daily dose (about 480 mg) of dimethyl fumarate, monomethyl fumarate, or a combination thereof. This patent introduces a specific dosage limitation not present in the earlier asserted patents. (Compl. Ex. F, ’514 Patent, Abstract; col. 28:57-65).
  • Asserted Claims: Independent claim 1 is asserted. (Compl. ¶¶103-105).
  • Accused Features: Defendants' ANDA product, which is a generic version of Tecfidera® available in 120 mg and 240 mg strengths, is accused of infringing this dosage-specific method patent. (Compl. ¶10, 100).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendants' generic dimethyl fumarate delayed-release capsules in 120 mg and 240 mg dosage strengths, for which Defendants submitted ANDA No. 210285 to the FDA. (Compl. ¶¶10, 28).
  • Functionality and Market Context: The accused product is an oral pharmaceutical intended for the treatment of relapsing forms of multiple sclerosis. (Compl. ¶¶10, 26). As a generic product submitted through an ANDA, it is intended to be a lower-cost, bioequivalent version of Plaintiffs' branded drug, Tecfidera®, and would compete directly with it upon FDA approval. (Compl. ¶27). The complaint alleges that the acts related to the ANDA filing were done with the cooperation and participation of both Stason Pharmaceuticals and Sawai Pharmaceutical. (Compl. ¶12). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 6,509,376 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 Defendants have submitted an ANDA seeking approval to manufacture and sell dimethyl fumarate delayed-release capsules. (Compl. Ex. A, ’376 Patent, col. 4:33-38). ¶28 col. 4:33-38
comprising one or more dialkyl fumarates of the formula... wherein R1 and R2... represent a... C1-20 alkyl radical... The accused generic products are alleged to contain 120 mg and 240 mg of dimethyl fumarate, which is a dialkyl fumarate covered by the claimed formula. (Compl. Ex. A, ’376 Patent, col. 4:1-9). ¶28 col. 3:67-col. 4:27
for use in... therapy of autoimmune diseases such as polyarthritis, multiple sclerosis... The accused products are intended for the treatment of relapsing forms of multiple sclerosis, an autoimmune disease listed in the claim. (Compl. Ex. A, ’376 Patent, col. 4:53-59). ¶10, ¶26 col. 4:53-59
  • Identified Points of Contention:
    • Scope Questions: The primary point of contention may be whether the Defendants' "delayed-release capsules" meet the claim limitation "in the form of microtablets or micropellets." The complaint does not specify the physical form of the dimethyl fumarate within the accused capsules, raising the question of whether it consists of compressed microtablets, simple pellets, or another formulation that might not read on the claim language.

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 The accused generic product is labeled for use in treating relapsing forms of multiple sclerosis, and Defendants allegedly will encourage this use by physicians and patients. (Compl. Ex. B, ’999 Patent, col. 3:55-58). ¶48 col. 3:55-58
comprising treating a patient... with an amount of a pharmaceutical preparation effective for treating said multiple sclerosis Defendants' product label, which is required to copy the Tecfidera® label, will instruct patients on an effective dosing regimen for treating multiple sclerosis. (Compl. Ex. B, ’999 Patent, col. 4:40-49). ¶48 col. 4:40-49
wherein the only active ingredient for the treatment of multiple sclerosis present in said pharmaceutical preparation is dimethyl fumarate. The accused product is a generic version of Tecfidera®, which contains dimethyl fumarate as its active ingredient for treating multiple sclerosis. (Compl. Ex. B, ’999 Patent, col. 3:55-58). ¶27, ¶28 col. 3:55-58
  • Identified Points of Contention:
    • Scope Questions: Analysis will likely focus on the term "only active ingredient." The question may arise as to whether any excipients in the Defendants' formulation could be characterized as having a therapeutic effect, which might allow Defendants to argue non-infringement.
    • Technical Questions: For this method claim, infringement by the Defendants will be indirect. The central question will be whether the complaint provides sufficient factual allegations to support the knowledge and specific intent required for a claim of induced infringement, such as evidence from proposed product labeling or instructions.

V. Key Claim Terms for Construction

  • The Term: "microtablets or micropellets" (’376 Patent, claim 1)

  • Context and Importance: This term is critical to the scope of the composition claims in the ’376 and ’393 patents. Infringement will depend on whether the physical formulation inside Defendants' capsules meets this definition. Practitioners may focus on this term because a formulation consisting of, for example, a simple powder or granules might not be considered "microtablets."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification suggests that pellets can be formed by spraying an active ingredient onto "nonpareilles pellets," a process that may result in a less precisely structured form than a compressed tablet. (Compl. Ex. A, ’376 Patent, col. 7:13-24).
    • Evidence for a Narrower Interpretation: Example 1 and Example 2 of the specification describe a process of compressing a powder mixture "to obtain convex tablets having a gross weight of 10.0 mg and a diameter of 2.0 mm," suggesting a specifically manufactured, compressed form. (Compl. Ex. A, ’376 Patent, col. 6:9-13, 64-67).

  • The Term: "only active ingredient" (’999 Patent, claim 1)

  • Context and Importance: The scope of the method claims in the ’999 and ’840 patents hinges on this term. Defendants could potentially avoid infringement if their formulation contains another substance that could be characterized as an "active ingredient."

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The term is not explicitly defined, leaving open the possibility that any component with a known physiological effect, even if primarily an excipient, could be argued to be an "active ingredient."
    • Evidence for a Narrower Interpretation: The patent's detailed description focuses exclusively on the therapeutic properties of dialkyl fumarates for treating autoimmune disease. (Compl. Ex. B, ’999 Patent, col. 3:34-53). This context suggests the term is meant to distinguish the claimed therapeutic agent (dimethyl fumarate) from pharmaceutically inert carriers or excipients.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval, Defendants will induce and contribute to infringement of the method claims (’999, ’001, ’840, ’514 patents). The basis for this allegation is that Defendants' product labeling, which under ANDA regulations must copy the FDA-approved labeling for Tecfidera®, will instruct physicians and patients to use the generic product in a manner that directly infringes the patented methods of treatment. (Compl. ¶¶48-49, 63-64, 78-79, 106-107).
  • Willful Infringement: The complaint does not include an explicit claim for willful infringement. However, it alleges that Defendants have had "actual knowledge" of each asserted patent since at least the date of the May 31, 2017 Notice Letter, which could form the basis for a future willfulness allegation. (Compl. ¶¶30, 44, 59, 74, 89, 102).

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

  • A core issue will be one of formulation scope: can the term "microtablets or micropellets," as used in the composition patents, be construed to cover the formulation contained within the Defendants' accused "delayed-release capsules"? The resolution will depend on claim construction and evidence regarding the physical structure of the accused generic product.
  • A second central question is one of induced infringement: does the act of submitting an ANDA with proposed labeling that mirrors the innovator's FDA-approved label suffice to establish the specific intent required to induce infringement of the asserted method-of-use patents?
  • Finally, a key issue for the later-issued method patents will be dosage scope: does the proposed dosing regimen for the accused generic product, as dictated by its bioequivalence to Tecfidera®, fall within the specific dosage limitations claimed in the ’514 patent?