DCT

1:18-cv-01115

Shire NPS Pharma Inc v. Par Pharmaceutical Companies Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01115, D. Del., 07/28/2018
  • Venue Allegations: Plaintiff alleges venue is proper because Defendant entities are incorporated in Delaware, and thus reside in the district. It is also alleged that Defendants did not dispute venue in a related action involving the same product and patent family.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Teduglutide for injection constitutes infringement of eight patents covering methods of treating Short Bowel Syndrome.
  • Technical Context: The patents relate to methods of using teduglutide, a glucagon-like peptide-2 (GLP-2) analog, to treat adult patients with Short Bowel Syndrome (SBS), a condition of malabsorption often requiring intravenous nutritional support.
  • Key Procedural History: The complaint references a "Related Action" (1:17-cv-00397) involving patents in the same family and the same ANDA product. In that action, ownership of the ANDA was transferred from Ambio, Inc. to Defendant Par Sterile Products, LLC.

Case Timeline

Date Event
2004-11-01 Earliest Patent Priority Date ('655, '656, '658, '835, '837, '014, '016, '334 Patents)
2012-12-21 Plaintiff's New Drug Application for GATTEX® approved
2017-02-28 Plaintiff received first notice letter regarding ANDA No. 210023
2017-04-10 Plaintiff filed the "Related Action"
2017-04-21 Par Sterile Products, LLC accepted ownership of ANDA No. 210023
2018-05-15 '655 Patent Issued
2018-05-15 '656 Patent Issued
2018-05-15 '658 Patent Issued
2018-05-22 '835 Patent Issued
2018-05-22 '837 Patent Issued
2018-05-29 '014 Patent Issued
2018-05-29 '016 Patent Issued
2018-06-05 '334 Patent Issued
2018-06-27 Plaintiff received Notice Letter regarding the Patents-in-Suit
2018-07-28 Complaint Filing Date

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

U.S. Patent No. 9,968,655 - "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity"

The Invention Explained

  • Problem Addressed: Patients with Short Bowel Syndrome (SBS) suffer from malabsorption due to surgical resection of the small intestine, leading to malnutrition and dehydration that often requires life-long, expensive, and complication-prone parenteral nutrition (PN) ('655 Patent, col. 1:30-51). Treatments that can enhance the intestine's absorptive capacity are needed to reduce or eliminate the need for PN ('655 Patent, col. 1:48-51).
  • The Patented Solution: The invention is based on the discovery that administering a GLP-2 receptor agonist, such as teduglutide ([Gly2]hGLP-2), enhances intestinal absorption in a specific subgroup of SBS patients: those who retain at least a portion of their colon in continuity with their remnant small intestine ('655 Patent, col. 2:17-24). This finding was not obvious because these "colon-in-continuity" patients already have elevated natural levels of GLP-2, suggesting that adding more via a drug might not provide further benefit ('655 Patent, col. 2:8-15).
  • Technical Importance: The invention provides a targeted therapy for a specific SBS patient population, offering a method to improve their intestinal function and potentially reduce their dependence on parenteral nutrition ('655 Patent, col. 1:48-51).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the '655 Patent without specifying which claims are at issue (Compl. ¶68). The analysis below uses independent claim 1 as a representative example.
  • Claim 1: A method with the following essential elements:
    • Treating an adult human patient having short bowel syndrome secondary to volvulus;
    • The patient receives parenteral nutrition each week;
    • The patient presents with colon-in-continuity with remnant small intestine;
    • The method comprises administering [Gly2]hGLP-2 (teduglutide);
    • The administration uses a dosing regimen effective to reduce or eliminate the weekly amount of parenteral nutrition received by the patient.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 9,968,656 - "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity"

The Invention Explained

  • Problem Addressed: As described for the '655 Patent, the invention addresses the need for treatments for SBS patients that can increase intestinal absorption and decrease reliance on parenteral nutrition ('656 Patent, col. 1:30-51).
  • The Patented Solution: This patent, like the '655 Patent, covers a method of treating SBS patients who have colon-in-continuity with a GLP-2 receptor agonist. The solution enhances the patient's own ability to absorb fluids and nutrients, demonstrated by an increase in wet weight absorption ('656 Patent, col. 2:17-24, 15:39-47).
  • Technical Importance: The invention provides a method to achieve a specific, measurable clinical benefit—increased wet weight absorption—in a targeted SBS patient population, which is a direct indicator of improved intestinal function ('656 Patent, col. 4:51-54).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the '656 Patent (Compl. ¶92). The analysis below uses independent claim 1 as a representative example.
  • Claim 1: A method with the following essential elements:
    • Treating an adult human patient having short bowel syndrome with colon-in-continuity and at least about 50 cm of remnant small intestine;
    • The patient receives an amount of parenteral nutrition each week;
    • The method comprises administering [Gly2]hGLP-2 (teduglutide);
    • The administration uses a dosing regimen effective to increase wet weight absorption compared to a baseline.
  • The complaint does not explicitly reserve the right to assert dependent claims.

Multi-Patent Capsule: U.S. Patent No. 9,968,658

  • Patent Identification: U.S. Patent No. 9,968,658, "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity," issued May 15, 2018.
  • Technology Synopsis: The patent describes methods for treating a specific subset of SBS patients—those with elevated basal levels of endogenous GLP-2 and who are dependent on parenteral nutrition—by administering a GLP-2 receptor agonist. The treatment is intended to reduce or eliminate the patient's weekly parenteral nutrition requirement ('658 Patent, col. 2:17-24, 15:20-29).
  • Asserted Claims: One or more claims (Compl. ¶116). Independent claims are 1, 6, and 11.
  • Accused Features: The method of using the Defendants' ANDA Product as will be instructed by its proposed product labeling for the treatment of adult SBS patients (Compl. ¶¶ 121-122).

Multi-Patent Capsule: U.S. Patent No. 9,974,835

  • Patent Identification: U.S. Patent No. 9,974,835, "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity," issued May 22, 2018.
  • Technology Synopsis: The patent claims a method for treating SBS patients whose condition is secondary to Crohn's disease and who have colon-in-continuity. The administration of a GLP-2 receptor agonist is claimed to be effective in reducing or eliminating the patient's need for weekly parenteral nutrition ('835 Patent, Claim 1).
  • Asserted Claims: One or more claims (Compl. ¶140). Independent claims are 1 and 6.
  • Accused Features: The method of using the Defendants' ANDA Product as will be instructed by its proposed product labeling for the treatment of adult SBS patients, including those with Crohn's disease (Compl. ¶¶ 145-146).

Multi-Patent Capsule: U.S. Patent No. 9,974,837

  • Patent Identification: U.S. Patent No. 9,974,837, "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity," issued May 22, 2018.
  • Technology Synopsis: The patent claims a method for treating SBS patients who do not have inflammatory bowel disease but still require parenteral nutrition. The method involves administering a GLP-2 receptor agonist to patients with colon-in-continuity to increase their wet weight absorption ('837 Patent, Claim 1).
  • Asserted Claims: One or more claims (Compl. ¶164). Independent claim is 1.
  • Accused Features: The method of using the Defendants' ANDA Product as will be instructed by its proposed product labeling for the treatment of adult SBS patients (Compl. ¶¶ 169-170).

Multi-Patent Capsule: U.S. Patent No. 9,981,014

  • Patent Identification: U.S. Patent No. 9,981,014, "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity," issued May 29, 2018.
  • Technology Synopsis: The patent claims a method for treating SBS patients whose condition is secondary to multiple strictures from adhesions or radiation. The method involves administering a GLP-2 receptor agonist to patients with colon-in-continuity to reduce their need for parenteral nutrition ('014 Patent, Claim 1).
  • Asserted Claims: One or more claims (Compl. ¶188). Independent claims are 1 and 6.
  • Accused Features: The method of using the Defendants' ANDA Product as will be instructed by its proposed product labeling for the treatment of adult SBS patients (Compl. ¶¶ 193-194).

Multi-Patent Capsule: U.S. Patent No. 9,981,016

  • Patent Identification: U.S. Patent No. 9,981,016, "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity," issued May 29, 2018.
  • Technology Synopsis: The patent claims a method for treating SBS patients whose condition is secondary to mesenteric infarction. The method involves administering a GLP-2 receptor agonist to patients with colon-in-continuity to increase their wet weight absorption compared to baseline ('016 Patent, Claim 1).
  • Asserted Claims: One or more claims (Compl. ¶212). Independent claim is 1.
  • Accused Features: The method of using the Defendants' ANDA Product as will be instructed by its proposed product labeling for the treatment of adult SBS patients (Compl. ¶¶ 217-218).

Multi-Patent Capsule: U.S. Patent No. 9,987,334

  • Patent Identification: U.S. Patent No. 9,987,334, "Treatment of Short Bowel Syndrome Patients With Colon-in-Continuity," issued June 5, 2018.
  • Technology Synopsis: The patent claims a method for treating SBS patients whose condition is secondary to a non-malignant disease (such as Crohn's, vascular ischemic disease, etc.). The method involves administering a GLP-2 receptor agonist to patients with colon-in-continuity to reduce their need for parenteral nutrition ('334 Patent, Claim 1).
  • Asserted Claims: One or more claims (Compl. ¶236). Independent claims are 1 and 6.
  • Accused Features: The method of using the Defendants' ANDA Product as will be instructed by its proposed product labeling for the treatment of adult SBS patients (Compl. ¶¶ 241-242).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is Defendants' generic "Teduglutide for Injection, 5 mg/vial," for which Defendants have filed Abbreviated New Drug Application (ANDA) No. 210023 with the FDA (Compl. ¶17). This product is referred to as the "ANDA Product" (Compl. ¶17).

Functionality and Market Context

  • The ANDA Product is a generic version of Plaintiff's GATTEX®, a GLP-2 analog indicated for the treatment of adult patients with Short Bowel Syndrome who are dependent on parenteral support (Compl. ¶¶ 35-36). The complaint alleges that Defendants' proposed labeling for the ANDA Product copies the approved label for GATTEX and that Defendants intend to market the product for the same indication (Compl. ¶48). The act of infringement alleged under 35 U.S.C. § 271(e)(2)(A) is the filing of the ANDA itself for the purpose of obtaining approval to market this generic drug before the expiration of the Patents-in-Suit (Compl. ¶68).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or detailed infringement contentions. The infringement theory is based on inducement, alleging that the proposed label for the ANDA Product will instruct medical professionals and patients to use the generic drug in a manner that directly infringes the claimed methods. The following charts summarize this theory for the representative independent claims of the two lead patents.

  • 9,968,655 Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating an adult human patient having short bowel syndrome secondary to volvulus, The proposed labeling for the ANDA Product will allegedly instruct its use for treating adult SBS patients, which would include those whose condition is secondary to volvulus. ¶¶48, 73, 74 col. 3:1-3
who receives parenteral nutrition each week, The proposed labeling will allegedly be for the same indication as GATTEX®, which is for patients dependent on parenteral support. ¶¶36, 48 col. 3:3-5
and who presents with colon-in-continuity with remnant small intestine, The instructions will allegedly lead to the treatment of the general population of SBS patients, which includes the sub-population with colon-in-continuity. ¶¶48, 73, 74 col. 3:16-21
said method comprising administering [Gly2]hGLP-2 to said patient The ANDA Product contains Teduglutide, which is [Gly2]hGLP-2, and the proposed labeling will instruct its administration to patients. ¶¶17, 73 col. 2:34-36
using a dosing regimen effective to reduce or eliminate said weekly amount of parenteral nutrition received by said patient. The proposed label will allegedly instruct a dosing regimen that, when followed, will result in the claimed therapeutic outcome of reducing or eliminating the need for parenteral nutrition. ¶¶48, 73 col. 4:51-54
  • 9,968,656 Infringement Allegations
Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating an adult human patient having short bowel syndrome with colon-in-continuity and at least about 50 cm of remnant small intestine The proposed labeling will allegedly instruct use in the indicated SBS population, which includes patients meeting these anatomical criteria. ¶¶48, 73, 74 col. 3:42-44
and who receives an amount of parenteral nutrition each week, The proposed labeling will allegedly be for the same indication as GATTEX®, which is for patients dependent on parenteral support. ¶¶36, 48 col. 3:3-5
said method comprising administering [Gly2]hGLP-2 to said patient The ANDA Product contains Teduglutide ([Gly2]hGLP-2), and the proposed label will instruct its administration. ¶¶17, 73 col. 2:34-36
using a dosing regimen effective to increase wet weight absorption compared to a baseline wet weight absorption by said patient. The proposed label will allegedly instruct a dosing regimen that, when followed, will result in the claimed therapeutic outcome of increased wet weight absorption. ¶¶48, 73 col. 4:51-54
  • Identified Points of Contention:
    • Scope Questions: A central question will be whether the patient population defined by the Defendants' proposed label is coextensive with the specific patient populations recited in the claims. For example, for the '655 Patent, does the label's indication for general SBS treatment inherently instruct use in the narrower claimed group whose SBS is "secondary to volvulus"?
    • Technical Questions: The complaint does not provide the proposed ANDA label. A key evidentiary question will be whether the specific instructions for use on that label, once produced in discovery, meet every limitation of the asserted claims, particularly the functional limitations requiring that the dosing regimen be "effective to reduce or eliminate...parenteral nutrition" or "effective to increase wet weight absorption."

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of specific terms that may be in dispute. However, based on the asserted claims, the following terms may be central to the case.

  • The Term: "colon-in-continuity" ('655 Patent, Claim 1; '656 Patent, Claim 1)

  • Context and Importance: This term defines the core patient population for all asserted patents. Its construction will determine the scope of the invention and whether the patients who will be treated according to the accused label fall within that scope. Practitioners may focus on this term because the patents' alleged novelty stems from treating this specific group.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification states that candidates are those who "retain, in continuity with remnant small intestine, at least some length of their colon, such as at least about 25%" ('655 Patent, col. 3:16-19). This language suggests any functional connection qualifies.
    • Evidence for a Narrower Interpretation: The patent distinguishes this group from patients with a jejunostomy or ileostomy, where if any colon remains, "it is not in continuity with the remnant small intestine" ('655 Patent, col. 3:13-15). This could be used to argue that the connection must meet certain functional criteria beyond a simple surgical anastomosis.

  • The Term: "dosing regimen effective to reduce or eliminate said weekly amount of parenteral nutrition" ('655 Patent, Claim 1)

  • Context and Importance: This is a functional limitation that defines the required outcome of the claimed method. The dispute may turn on what level of "reduction" is legally sufficient and how that is measured. Defendants may argue their proposed dosing instructions do not guarantee this outcome for all patients, while Plaintiff may argue the instruction itself is sufficient for inducement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes a clinical study where treatment led to a "significant" increase in absorption, implying that a statistically significant or clinically meaningful reduction meets the limitation ('655 Patent, col. 9:6-11).
    • Evidence for a Narrower Interpretation: The claims require reduction or elimination. A defendant could argue that a regimen that only achieves a minor, clinically insignificant reduction does not meet the claim, or that the term requires the regimen to be effective in a substantial number of patients to whom it is administered.

VI. Other Allegations

  • Indirect Infringement: The complaint's primary infringement theory is indirect. It alleges that by distributing the ANDA Product with its corresponding labeling and package insert, Defendants will knowingly and intentionally induce third parties (e.g., physicians and patients) to perform the patented methods (Compl. ¶¶ 72, 75). It further alleges contributory infringement, stating the ANDA Product is a material part of the patented methods and is not a staple article of commerce suitable for substantial noninfringing uses (Compl. ¶76).
  • Willful Infringement: The complaint does not explicitly allege "willful infringement" but requests a judgment that the case is "exceptional" under 35 U.S.C. § 285, which could entitle Plaintiff to attorneys' fees (Compl. ¶78). This is based on the allegation that Defendants knew of the patents, as evidenced by their filing of a Paragraph IV certification, and "acted without a reasonable basis for believing that they would not infringe" (Compl. ¶78).

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

The resolution of this case will likely depend on the court's determination of several key issues that bridge claim interpretation and infringement analysis:

  • A core issue will be one of definitional scope: How will the court construe the specific patient populations defined in the various independent claims (e.g., "secondary to volvulus," "with elevated basal levels of endogenous GLP-2")? The outcome will determine whether the broader patient population targeted by the ANDA Product's likely label will be found to induce infringement of these narrower method claims.
  • A second key issue will be one of functional efficacy: What level of clinical evidence is required to meet the functional limitations in the claims, such as a "dosing regimen effective to reduce or eliminate...parenteral nutrition"? The case may turn on whether the mere instruction to follow a dosing regimen is sufficient for infringement, or if there must be proof that the regimen consistently produces the claimed outcome in the patient population.