DCT

1:17-cv-00397

Shire NPS Pharma Inc v. Par Pharmaceutical Companies Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:17-cv-00397, D. Del., 04/10/2017
  • Venue Allegations: Plaintiff alleges venue is proper in Delaware because Defendants conduct regular business in the state, derive substantial revenue from products used there, and, in the case of Par Pharmaceutical Companies, Inc., are incorporated in Delaware. The complaint also notes Par Pharmaceutical, Inc. has previously submitted to the jurisdiction of the Delaware court in other matters.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's drug GATTEX® constitutes an act of infringement of three patents directed to pharmaceutical formulations of a GLP-2 analog and methods of treatment for Short Bowel Syndrome.
  • Technical Context: The technology relates to treatments for Short Bowel Syndrome (SBS), a malabsorptive condition often requiring parenteral nutritional support, using a glucagon-like peptide-2 (GLP-2) receptor agonist to improve intestinal function.
  • Key Procedural History: The action was triggered by Defendants' submission of ANDA No. 210023 with a Paragraph IV certification, asserting that the patents-in-suit are invalid or will not be infringed by their proposed generic product. Plaintiff received a notice letter regarding the ANDA filing on February 28, 2017. Subsequent to the filing of this complaint, U.S. Patent No. 7,056,886 was the subject of Inter Partes Review (IPR) proceedings (IPR2015-00990, IPR2015-01093), which resulted in the cancellation of all asserted claims.

Case Timeline

Date Event
1999-12-30 Earliest Priority Date for U.S. Patent No. 7,056,886
2004-11-01 Earliest Priority Date for U.S. Patent Nos. 7,847,061 and 9,060,992
2006-06-06 Issue Date of U.S. Patent No. 7,056,886
2010-12-07 Issue Date of U.S. Patent No. 7,847,061
2012-12-21 FDA Approval of Plaintiff's New Drug Application for GATTEX®
2015-04-01 Filing of IPR Petition against the '886 Patent (IPR2015-00990)
2015-04-23 Filing of IPR Petition against the '886 Patent (IPR2015-01093)
2015-06-23 Issue Date of U.S. Patent No. 9,060,992
2017-02-28 Plaintiff receives Defendants' Paragraph IV Notice Letter
2017-04-10 Complaint Filing Date

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

U.S. Patent No. 7,056,886 - "GLP-2 Formulations"

The Invention Explained

  • Problem Addressed: The patent describes the technical challenge that therapeutic peptides are often unstable and prone to degradation, aggregation, and precipitation over time, which complicates their formulation for storage and parenteral administration (Compl. Ex. A, '886 Patent, col. 1:11-20).
  • The Patented Solution: The invention claims to solve this problem by providing a specific formulation that enhances the stability of Glucagon-like peptide-2 (GLP-2) and its analogs. The patented solution comprises a combination of the GLP-2 peptide with a phosphate buffer to maintain pH in a stable range, the amino acid L-histidine as a specific stabilizer, and mannitol as a bulking agent, particularly for lyophilized (freeze-dried) preparations (Compl. Ex. A, '886 Patent, col. 2:7-14, 39-44).
  • Technical Importance: Creating a stable, long-shelf-life formulation is a critical step for the commercial viability of any peptide therapeutic, as it enables reliable manufacturing, distribution, and clinical use (Compl. Ex. A, '886 Patent, col. 1:39-44).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the '886 patent without specifying them (Compl. ¶56). At the time of filing, Claim 1 was a key independent composition claim.
  • Independent Claim 1 (as issued) included the following essential elements:
    • A medically useful amount of a naturally occurring GLP-2 or an analog thereof;
    • A phosphate buffer in an amount sufficient to adjust the pH of the formulation to a physiologically tolerable level;
    • L-histidine; and
    • A bulking agent selected from the group consisting of mannitol and sucrose.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 7,847,061 - "Treatment of Short Bowel Syndrome Patients with Colon-in-Continuity"

The Invention Explained

  • Problem Addressed: The patent addresses the treatment of a specific subgroup of patients with Short Bowel Syndrome (SBS). It notes the potential for added benefit from GLP-2 therapy in SBS patients who retain a connection between their colon and small intestine ("colon-in-continuity") was considered "not obvious" because these patients already exhibit elevated endogenous levels of GLP-2 (Compl. Ex. B, '061 Patent, col. 2:61-66).
  • The Patented Solution: The invention is based on the discovery that administering a GLP-2 receptor agonist, such as teduglutide, to SBS patients with colon-in-continuity provides significant clinical benefit by enhancing intestinal absorption, particularly "absolute wet weight absorption" (Compl. Ex. B, '061 Patent, col. 2:4-8, 45-50). Figure 1 of the patent graphically depicts the measured changes in fecal output, intestinal absorption, and urine output for patients at baseline, during treatment, and at follow-up, illustrating the claimed therapeutic effect (Compl. Ex. B, '061 Patent, Fig. 1).
  • Technical Importance: This finding was significant because it identified a specific patient population that could benefit from GLP-2 therapy, contrary to what might have been expected based on their underlying physiology (Compl. Ex. B, '061 Patent, col. 2:40-45).

Key Claims at a Glance

  • The complaint asserts infringement of one or more claims of the '061 patent (Compl. ¶76). Claim 1 is the sole independent claim.
  • Independent Claim 1 includes the following essential elements:
    • A method for enhancing intestinal absorption in a patient with short bowel syndrome presenting with colon in continuity with remnant small intestine, comprising the steps of:
    • selecting for treatment a short bowel syndrome patient presenting with colon in continuity with remnant small intestine; and
    • treating said patient with a GLP-2 receptor agonist using a dosing regimen effective to enhance intestinal absorption by said patient.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,060,992 - "Treatment of Short Bowel Syndrome Patients with Colon-in-Continuity"

  • Patent Identification: U.S. Patent No. 9,060,992, "Treatment of Short Bowel Syndrome Patients with Colon-in-Continuity," issued June 23, 2015 (Compl. ¶35).
  • Technology Synopsis: This patent, which shares a specification with the '061 patent, is also directed to methods of treating SBS patients with colon-in-continuity. The invention is similarly based on the surprising discovery that administering a GLP-2 receptor agonist enhances intestinal absorption in this patient population, despite their elevated baseline levels of endogenous GLP-2. This patent further refines the patient population by requiring that they produce at least about 10% of the endogenous GLP-2 levels of a healthy individual (Compl. Ex. C, '992 Patent, col. 2:57-66; Claim 1).
  • Asserted Claims: The complaint asserts infringement of one or more claims (Compl. ¶94). The key independent claim is Claim 1.
  • Accused Features: The accused feature is the proposed method of use for Defendants' generic teduglutide product. The complaint alleges that the product's labeling will induce physicians to prescribe, and patients to use, the drug for the treatment of SBS in a manner that infringes the claimed method, specifically by treating patients with colon-in-continuity (Compl. ¶97-98).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Defendants' ANDA Product," a generic version of Teduglutide for Injection, 5 mg/vial, for which Defendants seek FDA approval under Abbreviated New Drug Application (ANDA) No. 210023 (Compl. ¶6, 37).

Functionality and Market Context

The ANDA product is a generic equivalent of Plaintiff's branded drug, GATTEX®. GATTEX is a lyophilized powder for reconstitution, containing a glucagon-like peptide-2 (GLP-2) analog, indicated for the treatment of adult patients with Short Bowel Syndrome (SBS) who depend on parenteral support (Compl. ¶31-32). Defendants' filing of the ANDA seeks approval to engage in the commercial manufacture and sale of their generic product for the same indication prior to the expiration of Plaintiff's patents (Compl. ¶37, 55).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain explicit claim charts. The following tables summarize the infringement allegations as implied by the complaint, which asserts that Defendants' ANDA product is a generic version of Plaintiff's GATTEX® product and that its proposed use aligns with the patented methods.

U.S. Patent No. 7,056,886 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a medically useful amount of a naturally occurring GLP-2 or an analog thereof The ANDA product contains teduglutide, which is an analog of GLP-2 ([Gly2]hGLP-2). ¶32, 37 col. 12:11-13
a phosphate buffer in an amount sufficient to adjust the pH of the formulation... The ANDA product is alleged to be a formulation claimed by the '886 patent, which, for the branded equivalent, includes a phosphate buffer. ¶36, 52 col. 12:14-17
L-histidine The ANDA product is alleged to be a formulation claimed by the '886 patent, which, for the branded equivalent, includes L-histidine. ¶36, 52 col. 12:18
a bulking agent selected from the group consisting of mannitol and sucrose The ANDA product is alleged to be a formulation claimed by the '886 patent, which, for the branded equivalent, includes the bulking agent mannitol. ¶36, 52 col. 12:19-21

U.S. Patent No. 7,847,061 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
selecting for treatment a short bowel syndrome patient presenting with colon in continuity with remnant small intestine The proposed labeling for Defendants' ANDA product will allegedly instruct and encourage physicians to treat SBS patients, which will include the sub-population with colon-in-continuity. ¶79 col. 14:56-59
treating said patient with a GLP-2 receptor agonist using a dosing regimen effective to enhance intestinal absorption The proposed labeling for the ANDA product, which contains the GLP-2 agonist teduglutide, will allegedly instruct its administration to SBS patients in a manner that enhances intestinal absorption. ¶32, 79 col. 14:60-63

Identified Points of Contention

  • Scope Questions: For the '061 and '992 patents, a primary question is whether Defendants' proposed label will actively induce infringement of the method claims. The analysis will focus on whether the label's language specifically instructs or encourages use in the claimed "colon-in-continuity" patient sub-population, or if it only contains a general indication for SBS, leaving the selection of specific patient types to the physician's judgment.
  • Technical Questions: For the '886 patent, a central question at the time of filing would have been whether the specific formulation detailed in Defendants' confidential ANDA submission—including its excipients, concentrations, and pH—falls within the scope of the patent's claims. However, this is superseded by the subsequent cancellation of all asserted claims in IPR proceedings.

V. Key Claim Terms for Construction

Analysis of claim terms for the '886 Patent is moot, as all asserted claims were subsequently cancelled in Inter Partes Review proceedings. For the '061 and '992 patents, which share a common specification, the construction of the following terms will be critical.

  • The Term: "colon in continuity with remnant small intestine"
  • Context and Importance: This term defines the specific patient population central to the asserted method claims. The scope of infringement will depend entirely on whether the patients who will foreseeably be treated with the generic drug fall within this definition. Practitioners may focus on this term because its precise scope dictates the universe of infringing acts.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes the patient group in general terms, stating "SBS patients selected for treatment ... are those who retain, in continuity with remnant small intestine, at least some length of their colon" (Compl. Ex. B, '061 Patent, col. 3:1-4). This language could support a broad definition covering any patient with an anatomical connection.
    • Evidence for a Narrower Interpretation: The detailed description of the clinical trials notes that patient candidates retained specific amounts, such as "at least about 25%" or "at least 50%" of their colon (Compl. Ex. B, '061 Patent, col. 3:2-4, 4:40). A defendant could argue this implies a narrower definition requiring a quantitatively significant portion of the colon to be present and functional.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement for all three patents, stating that by marketing and distributing their ANDA product with its accompanying label, package insert, and medication guide, Defendants will knowingly encourage and instruct physicians and patients to use the product in a manner that infringes the patented methods of treatment (Compl. ¶59, 79, 97). The complaint also alleges contributory infringement of the '886 patent, asserting the ANDA product is a material component of the claimed methods and is not a staple article of commerce (Compl. ¶60).

Willful Infringement

The complaint alleges that Defendants had knowledge of all three patents-in-suit, as evidenced by their filing of a Paragraph IV certification that specifically referenced each patent (Compl. ¶58, 78, 96). It further alleges that Defendants acted "without a reasonable basis for believing that they would not infringe," which forms the basis for a request that the case be found "exceptional" under 35 U.S.C. § 285, potentially entitling Plaintiff to attorneys' fees (Compl. ¶64, 82, 100).

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

  • A dispositive threshold question will be the legal finality of post-filing events: given that all asserted claims of the '886 patent were cancelled in Inter Partes Review after the complaint was filed, the court must first determine if any viable cause of action related to that patent remains.
  • A central issue for the surviving '061 and '992 patents will be one of induced infringement: does the specific language of the Defendants' proposed drug label meet the legal standard for actively encouraging or instructing use in the claimed "colon-in-continuity" patient population, or does it only provide a general indication for Short Bowel Syndrome?
  • Underlying the inducement analysis, the case may turn on a key question of claim construction: will the term "colon in continuity" be construed broadly to encompass any patient with a connected colon, or will it be narrowed to require a more specific and substantial percentage of remaining colon, as described in the patent’s clinical trial examples?