DCT

1:18-cv-01224

Horizon Therap LLC v. Par Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01224, D. Del., 08/10/2018
  • Venue Allegations: Venue is alleged to be proper in Delaware as Defendant Par Pharmaceutical Companies, Inc. is incorporated in Delaware, and both defendants are alleged to conduct substantial business in the state.
  • Core Dispute: Plaintiff alleges that Defendants' filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's drug RAVICTI® constitutes an act of infringement of a patent covering methods for dosing ammonia-scavenging drugs.
  • Technical Context: The technology concerns therapeutic methods for managing dangerously high ammonia levels in patients with urea cycle disorders (UCDs), a group of rare but serious metabolic diseases.
  • Key Procedural History: The complaint notes that the patent-in-suit, U.S. Patent No. 8,642,012, was previously challenged by Defendant Par Pharmaceutical, Inc. in an inter partes review (IPR). The Patent Trial and Appeal Board (PTAB) found that Par failed to prove any claims unpatentable, and this decision was summarily affirmed by the U.S. Court of Appeals for the Federal Circuit. This history may raise a question of issue preclusion regarding patent validity in the current litigation.

Case Timeline

Date Event
2008-08-29 U.S. Patent No. 8,642,012 Priority Date
2014-02-04 U.S. Patent No. 8,642,012 Issue Date
2014-03-12 Defendant sends Paragraph IV Certification letter
2014-04-23 Prior infringement suit filed in E.D. Texas
2015-04-29 Defendant files IPR petition challenging the '012 patent
2015-12-14 E.D. Texas litigation is stayed pending IPR
2016-11-03 PTAB issues Final Written Decision finding claims not unpatentable
2018-06-18 Federal Circuit affirms PTAB decision
2018-07-25 Federal Circuit issues mandate
2018-08-09 Plaintiff voluntarily dismisses E.D. Texas suit
2018-08-10 Complaint Filing Date (D. Del.)

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

U.S. Patent No. 8,642,012 - Methods of Treatment Using Ammonia-Scavenging Drugs

Issued February 4, 2014

The Invention Explained

  • Problem Addressed: The patent's background describes that conventional methods for dosing ammonia-scavenging drugs are unreliable. Specifically, monitoring blood levels of the drug (e.g., phenylbutyrate or PBA) or its active metabolite (phenylacetic acid or PAA) does not accurately reflect the drug's effectiveness in removing ammonia. Furthermore, directly measuring blood ammonia levels is inconvenient and can be influenced by many factors other than the drug's action. (ʼ012 Patent, col. 1:28-44).
  • The Patented Solution: The invention provides a new method for dosing these drugs based on a more reliable metric: the amount of a waste product, phenylacetylglutamine (PAGN), excreted in the patient's urine. The method is refined by a key discovery that the in-vivo conversion of the administered drug to urinary PAGN is incomplete, with a "mean conversion...of about 60%." This efficiency factor is used to more accurately calculate the appropriate drug dosage needed to manage a patient's dietary protein intake. (ʼ012 Patent, Abstract; col. 41:17-26).
  • Technical Importance: This approach provided a more precise, metabolically-grounded method for managing a life-threatening condition, shifting the focus from unreliable blood concentration measurements to the actual therapeutic output of waste nitrogen removal. (ʼ012 Patent, col. 1:45-51).

Key Claims at a Glance

The complaint alleges infringement of "one or more claims" of the '012 patent without specifying them (Compl. ¶34). The patent contains two independent method claims, 1 and 8.

  • Independent Claim 1: A method of treating a patient with a urea cycle disorder (UCD), comprising the steps of:
    • Determining a target urinary PAGN output.
    • Calculating an effective initial dosage of a PAA prodrug (e.g., glycerol phenylbutyrate or phenylbutyric acid).
    • The calculation is based on a mean conversion of the prodrug to urinary PAGN of about 60%.
    • Administering the effective initial dosage.
  • Independent Claim 8: A method of administering a PAA prodrug to a UCD patient, comprising the steps of:
    • Administering a first dosage.
    • Determining urinary PAGN excretion.
    • Determining an effective dosage based on the PAGN excretion and a mean conversion rate of about 60%.
    • Administering the effective dosage.

III. The Accused Instrumentality

Product Identification

Defendants' proposed generic version of glycerol phenylbutyrate oral liquid, 1.1 gm/ml, which is the subject of ANDA No. 205742 ("Par Product") (Compl. ¶¶1, 16).

Functionality and Market Context

The Par Product is a generic equivalent of Plaintiff's RAVICTI® and is intended for use as a nitrogen-binding agent for the chronic management of UCDs (Compl. ¶¶5, 10). The infringement alleged is not based on the composition of the drug itself, but on the method of its use that will be directed by its product labeling. The complaint alleges, upon information and belief, that the proposed labeling for the Par Product "copies the FDA-approved label for RAVICTI®" and will instruct physicians and patients to use the product for the approved indication (Compl. ¶10).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not include a claim chart or the proposed product label. The infringement theory is based on inducement, alleging that the instructions on the Par Product's label will cause medical professionals and patients to perform the patented method.

'012 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a patient having a urea cycle disorder... The complaint alleges Defendants' proposed product is intended for this exact use and that its label will instruct medical practitioners to use it for this purpose. ¶10, ¶38 col. 41:17-18
calculating an effective initial dosage of a phenylacetic acid (PAA) prodrug...wherein the effective dosage of the PAA prodrug is calculated based on a mean conversion of PAA prodrug to urinary PAGN of about 60% The complaint alleges that the instructions on the proposed product label will encourage and instruct medical practitioners to perform the methods claimed in the '012 patent, which includes this specific calculation step. ¶39, ¶41 col. 41:19-24
and administering the effective initial dosage of the PAA prodrug to the patient. The complaint alleges the proposed label will instruct administration of the drug in a manner that, when combined with the other steps, constitutes infringement. ¶40 col. 41:25-26

Identified Points of Contention

  • Scope Questions: A central dispute will likely concern whether the instructions on Par's proposed label meet the specific limitations of the method claims. A key question for the court will be: Does the term "calculated based on a mean conversion...of about 60%" read on the dosing instructions provided in the Par Product's final approved labeling?
  • Technical Questions: An evidentiary question will be what proof Plaintiff can offer that following the instructions on the Par Product's label would necessarily result in a medical professional performing the specific "calculating" step as required by the claims. The outcome may depend on whether the label provides specific conversion factors or merely general dosing guidance.

V. Key Claim Terms for Construction

The Term: "mean conversion...of about 60%" (Claim 1)

  • Context and Importance: This term is the technical core of the claimed invention, distinguishing it from prior art methods that assumed 100% conversion or did not consider it. The definition of "about 60%" will be critical to the infringement analysis, as Par's label would need to instruct a calculation falling within the construed scope of this term.
  • Intrinsic Evidence for a Broader Interpretation: The patent specification discloses that conversion efficiency can vary, noting it was "about 60%...in UCD patients and about 75% conversion was seen in cirrhotic patients." ('012 Patent, col. 9:29-32). This could support construing "about 60%" to encompass a range of values.
  • Intrinsic Evidence for a Narrower Interpretation: The claims themselves recite "about 60%." The detailed description also uses this specific figure when describing how to determine a dosage, stating the dosage is "utilized at an estimated efficiency of 60%." ('012 Patent, col. 17:15-16). This may be used to argue for a narrower construction centered on the 60% value.

VI. Other Allegations

Indirect Infringement

The complaint is founded on allegations of indirect infringement. It pleads induced infringement by alleging Defendants' product label and marketing materials will knowingly "encourage, advise, instruct, [and] urge" medical professionals and patients to perform the patented methods (Compl. ¶¶38, 41). It also pleads contributory infringement, alleging the Par Product is a material part of the patented method and is not a staple article of commerce suitable for substantial noninfringing uses (Compl. ¶42).

Willful Infringement

The complaint requests a finding that the case is "exceptional" under 35 U.S.C. § 285, which can lead to an award of attorneys' fees (Compl. Prayer for Relief ¶F). This is based on the allegation that Defendants were aware of the '012 patent at least as of their notice letter dated March 12, 2014, and acted without a reasonable basis for believing they would not infringe (Compl. ¶44).

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

  • A central issue will be one of induced infringement: Will the language in Defendants' final, FDA-approved product label be found to actively instruct or encourage medical professionals to perform the full, multi-step calculation method recited in the asserted claims, particularly the step of using a "mean conversion...of about 60%"?
  • A key threshold question will be one of issue preclusion: Can Defendants mount a meaningful challenge to the validity of the '012 patent's claims, given that the same claims survived an IPR challenge brought by the same defendant, a decision that was subsequently affirmed by the Federal Circuit?