DCT

1:17-cv-00329

Salix Pharma v. Teva Pharmaceutical

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00329, D. Del., 03/27/2017
  • Venue Allegations: Venue is asserted based on Teva being a Delaware corporation with extensive, systematic contacts with the district, including registration with the Delaware Board of Pharmacy and substantial marketing and sales activities.
  • Core Dispute: Plaintiffs allege that Teva’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the ulcerative colitis drug Apriso® constitutes an act of patent infringement.
  • Technical Context: The lawsuit concerns oral, extended-release pharmaceutical formulations of mesalamine, a drug used for the long-term maintenance of remission in patients with ulcerative colitis.
  • Key Procedural History: This case was initiated under the Hatch-Waxman Act following Teva's submission of a Paragraph IV certification, alleging that the patent-in-suit is invalid, unenforceable, and/or not infringed by its proposed generic product. An Inter Partes Review (IPR) Certificate issued for the patent-in-suit on October 21, 2019, subsequent to the filing of this complaint, indicates that claims 1 and 16 were cancelled. This development raises a significant question regarding the continued viability of any action based on these specific claims.

Case Timeline

Date Event
2008-10-03 ’688 Patent Priority Date
2008-10-31 FDA approves NDA for Apriso®
2014-10-21 U.S. Patent No. 8,865,688 issues
2017-02-13 Teva sends Paragraph IV Notice Letter to Plaintiffs
2017-03-27 Complaint filed
2019-10-21 IPR Certificate issues cancelling claims 1 and 16 of the '688 patent

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

U.S. Patent No. 8,865,688 - "Compositions and Methods for Treatment of Bowel Diseases with Granulated Mesalamine," Issued October 21, 2014

The Invention Explained

  • Problem Addressed: The patent describes the challenge of treating ulcerative colitis (UC) with oral mesalamine, noting that the clinical efficacy is related to delivering the intact drug molecule to the colonic mucosa without premature breakdown in the digestive system (’688 Patent, col. 1:60-63). Existing delivery systems, such as those relying on pH-triggered coatings or time-dependent release, were described as having problems including premature release and sensitivity to food intake (’688 Patent, col. 2:3-8).
  • The Patented Solution: The invention claims methods for maintaining remission of UC by administering a specific granulated mesalamine formulation. This formulation uses a capsule containing granules that have a pH-dependent coating designed to dissolve at pH 6 or greater, which is typically reached in the terminal ileum and colon (’688 Patent, col. 14:26-35). This delayed release is combined with an extended-release polymer matrix core, which slowly and uniformly distributes the mesalamine throughout the lower gastrointestinal tract, ensuring high local availability at the site of disease (’688 Patent, col. 13:35-54).
  • Technical Importance: The claimed once-daily dosing regimen for maintaining remission addresses a significant issue in chronic disease management: patient compliance, which can be improved with simpler dosing schedules compared to multiple daily doses (’688 Patent, col. 12:30-34).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specifying which ones (Compl. ¶ 26). Independent claims 1 and 16 are the primary method claims. As noted, an IPR Certificate indicates these claims were cancelled after the complaint was filed.
  • Independent Claim 1 (Cancelled):
    • A method of maintaining the remission of ulcerative colitis in a subject
    • comprising administering to the subject a granulated mesalamine formulation comprising four capsules each comprising 0.375 g of granulated mesalamine
    • administered once per day in the morning, without food
    • wherein said method maintains remission of ulcerative colitis in a subject for a period of at least 6 months of treatment
    • wherein remission is defined as a DAI score of 0 or 1
    • the granulated mesalamine formulation is not administered with antacids
    • and wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Teva’s proposed generic version of Apriso®, described as "375 mg mesalamine oral extended release capsules" in its ANDA No. 209970 ("Teva's ANDA product") (Compl. ¶¶ 2, 20).

Functionality and Market Context

  • The complaint alleges that Teva's ANDA product is a generic version of Salix's Apriso® drug product (Compl. ¶ 2). As a generic equivalent, it is intended for the same indication: the maintenance of remission of ulcerative colitis in adults (Compl. ¶ 13). The act of infringement alleged is the filing of the ANDA itself, which seeks FDA approval to manufacture, use, and sell this generic product prior to the expiration of the ’688 Patent (Compl. ¶ 26).

IV. Analysis of Infringement Allegations

The complaint does not provide a detailed infringement analysis or claim chart. The infringement theory is based on 35 U.S.C. § 271(e)(2), where the submission of an ANDA for a generic drug covered by a patent is a statutory act of infringement. The analysis below outlines how the use of Teva's ANDA product, as would be directed by its FDA-approved label, is alleged to meet the elements of claim 1 of the ’688 Patent. No probative visual evidence provided in complaint.

’688 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of maintaining the remission of ulcerative colitis in a subject The complaint alleges Teva seeks approval for its ANDA product for the same indication as Apriso®, which is the maintenance of remission of ulcerative colitis (Compl. ¶13). ¶¶ 2, 13, 26 col. 2:56-59
comprising administering... a granulated mesalamine formulation comprising four capsules each comprising 0.375 g of granulated mesalamine Teva’s ANDA product is identified as a generic 375 mg mesalamine oral extended release capsule, and the standard dosage for Apriso® is 1.5 g/day (four 375 mg capsules). ¶¶ 2, 20, 23 col. 2:47-49
once per day in the morning, without food The complaint alleges Teva’s product is a generic version of Apriso®. The use of Teva's product as directed by its proposed label is alleged to meet this administration instruction, which is part of the patented method. ¶¶ 2, 26 col. 10:63-65
wherein said method maintains remission of ulcerative colitis in a subject for a period of at least 6 months of treatment The clinical trials described in the patent to support the invention were conducted over a six-month period. It is alleged the use of Teva's product would achieve this outcome. ¶ 26 col. 11:58-61
wherein remission is defined as a DAI score of 0 or 1 The patent defines remission according to a specific clinical index (DAI score). It is alleged that use of Teva's product will result in this clinical state, meeting the claim limitation. ¶ 26 col. 34:17-18
the granulated mesalamine formulation is not administered with antacids The patent explicitly teaches against co-administration with antacids because it could affect the pH-dependent coating. It is alleged that Teva's label will include this instruction or that the method will be practiced this way. ¶ 26 col. 10:2-3
and wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon. This limitation defines a specific pharmacokinetic/bioavailability outcome. It is alleged that Teva's product, as a bioequivalent generic, will exhibit this property when administered according to the method. ¶ 26 col. 13:52-54
  • Identified Points of Contention:
    • Scope Questions: The complaint does not specify which claims are asserted beyond "one or more." The cancellation of claims 1 and 16 via IPR raises the primary question of whether any asserted claims remain enforceable.
    • Technical Questions: Assuming a valid claim is asserted, a key question would be whether Teva's ANDA product and its proposed label will actually result in the specific outcomes required by the claims. For example, what evidence demonstrates that use of Teva's product achieves "remission... defined as a DAI score of 0 or 1" or results in "85% to 90% of the mesalamine reach[ing] the terminal ileum and colon"? These are highly specific clinical and pharmacokinetic parameters that Teva may argue its product does not meet, or that the patent fails to enable.

V. Key Claim Terms for Construction

  • The Term: "wherein remission is defined as a DAI score of 0 or 1"

    • Context and Importance: This term appears in independent claim 1 and defines the primary endpoint of the claimed method with reference to a specific clinical scale, the Sutherland Disease Activity Index (DAI). The construction of this term is critical because infringement requires that the administered generic product achieves this precise level of clinical remission. Teva could argue its product is not labeled for or does not achieve this specific outcome, or that the term renders the claim indefinite.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The body of the patent describes the goal of treatment as inducing and maintaining remission generally, which could support an argument that the DAI score is merely one example of how to measure remission (’688 Patent, col. 1:49-50).
      • Evidence for a Narrower Interpretation: The claim language uses the explicit phrase "is defined as," suggesting the DAI score is not merely an example but a required definition of the claimed "remission." The patent's detailed description of clinical trial results relies on this specific DAI scoring system to establish efficacy, reinforcing its definitional importance (’688 Patent, col. 17:5-15).

  • The Term: "wherein 85% to 90% of the mesalamine reaches the terminal ileum and colon"

    • Context and Importance: This limitation in claim 1 defines a required pharmacokinetic outcome of the method. Practitioners may focus on this term because it sets a high, specific bar for targeted drug delivery that could be a focal point for a non-infringement defense. Teva would likely argue that its product does not achieve this specific delivery profile or that the patent does not enable one of ordinary skill to achieve it reliably.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification generally discusses the goal of delivering the drug to the colon (’688 Patent, col. 1:60-63), which a party might argue should inform a more flexible interpretation of the specific numerical range.
      • Evidence for a Narrower Interpretation: The patent explicitly states that the formulation's release profile and pharmacokinetic data show "that 85% to 90% of drug reaches the diseased area" (’688 Patent, col. 13:52-54). This direct support suggests the numbers are a specific, intended limitation of the invention and not merely an approximation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Teva will actively induce infringement under 35 U.S.C. § 271(b) (Compl. ¶ 27). The factual basis for this allegation is that Teva intends to market its ANDA product with an FDA-approved product insert that will "direct physicians and patients in the use of Teva's ANDA product" in an infringing manner (Compl. ¶ 28).
  • Willful Infringement: The complaint does not use the word "willful," but it seeks enhanced damages and attorneys' fees for an "exceptional case" under 35 U.S.C. § 285 (Compl., Prayer for Relief ¶ G). The basis for this is Teva’s alleged knowledge of the ’688 Patent, as evidenced by its submission of the Paragraph IV certification letter prior to the lawsuit (Compl. ¶¶ 20, 30).

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

  1. Enforceability of Asserted Claims: The central and likely dispositive issue is the legal status of the asserted claims. Given that an IPR Certificate issued post-filing indicates the cancellation of independent claims 1 and 16, the primary question is whether Plaintiffs' infringement action, which is pleaded broadly against "one or more claims," can proceed on any surviving, un-cancelled claims from the ’688 patent.
  2. Definitional Scope and Proof: Should the case proceed on other claims, a core issue will be one of definitional scope: can Teva's generic product be proven to meet the highly specific clinical and pharmacokinetic limitations of the patent, such as achieving "remission... defined as a DAI score of 0 or 1" and delivering "85% to 90% of the mesalamine" to the specified location?
  3. Invalidity: A parallel question, raised by Teva's Paragraph IV certification but not detailed in the complaint, is whether the asserted claims are invalid for reasons such as obviousness or lack of enablement. The court would need to determine if one of ordinary skill in the art could achieve the claimed method, with its precise dosing and outcome parameters, based on the patent's disclosure and the prior art at the time.