DCT

1:16-cv-01066

United Therap Corp v. Par Sterile Products LLC

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:16-cv-01066, D. Del., 11/17/2016
  • Venue Allegations: Venue is asserted based on Defendants being incorporated or organized in Delaware.
  • Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) for a generic version of REMODULIN® (Treprostinil Sodium) Injection infringes five patents related to the drug's manufacturing process, formulation, and methods of use.
  • Technical Context: The technology concerns pharmaceutical compositions and manufacturing processes for treprostinil, a prostacyclin analog used to treat pulmonary arterial hypertension, a rare and serious condition involving high blood pressure in the arteries of the lungs.
  • Key Procedural History: The action was initiated in response to a Paragraph IV certification notice letter from the Defendant, dated October 3, 2016, challenging U.S. Patent Nos. 8,497,393 and 9,199,908. The complaint notes that the notice letter did not address U.S. Patent Nos. 7,999,007, 8,653,137, or 8,658,694. Notably, public records for the ’393 Patent, which are included in the provided documents, indicate that an Inter Partes Review (IPR2016-00006) was filed on October 2, 2015, and a certificate issued on October 22, 2019, cancelled all claims of that patent.

Case Timeline

Date Event
2002-05-01 REMODULIN® initially approved by FDA
2003-05-22 ’908 Patent earliest priority date
2007-09-07 ’007, ’137, and ’694 Patents earliest priority date
2007-12-17 ’393 Patent earliest priority date
2011-08-16 ’007 Patent issued
2014-02-18 ’137 Patent issued
2014-02-25 ’694 Patent issued
2014-07-30 ’393 Patent issued
2015-10-02 IPR filed against ’393 Patent
2015-12-01 ’908 Patent issued
2016-10-03 Par's Notice Letter sent to UTC
2016-11-17 Complaint filed
2019-10-22 IPR Certificate issues, cancelling all claims of ’393 Patent

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

U.S. Patent No. 8,497,393 - "Process to Prepare Treprostinil, the Active Ingredient in Remodulin®"

  • Issued: July 30, 2014.

The Invention Explained

  • Problem Addressed: The patent background describes the need for an efficient process for the large-scale synthesis of prostacyclin derivatives suitable for commercial production, noting that prior art methods often rely on purification by column chromatography, which is resource-intensive and generates significant waste (’393 Patent, col. 5:36-49).
  • The Patented Solution: The invention claims a process that avoids column chromatography by forming a salt of treprostinil, such as a diethanolamine salt, after hydrolysis of a nitrile intermediate (’393 Patent, col. 6:46-61). This salt can be isolated and purified through more efficient methods like crystallization before being converted back to the final high-purity treprostinil acid, making the process more economical, safer, and "greener" for commercial manufacturing (’393 Patent, col. 5:40-52).
  • Technical Importance: This process offers a method to simplify the commercial-scale manufacturing of a key pharmaceutical by replacing a costly and complex purification technique with a more scalable salt formation and crystallization step (’393 Patent, col. 5:40-52).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 and dependent claim 9 (Compl. ¶56).
  • Independent Claim 1 is a product-by-process claim directed to a product comprising treprostinil prepared by a specific multi-step process:
    • (a) Alkylating a benzindene triol compound (structure II) to produce a benzindene nitrile compound (structure III)
    • (b) Hydrolyzing the benzindene nitrile with a base
    • (c) Contacting the resulting product with a base B to form a salt
    • (d) Optionally reacting the salt with an acid to form the final treprostinil compound (’393 Patent, col. 18:50 - col. 20:2).

U.S. Patent No. 9,199,908 - "Compounds and Methods for Delivery of Prostacyclin Analogs"

  • Issued: December 1, 2015.

The Invention Explained

  • Problem Addressed: The patent addresses the low oral bioavailability of certain drugs, specifically noting that treprostinil free acid has an absolute oral bioavailability of less than 10%, which necessitates administration via more invasive routes like injection (’908 Patent, col. 1:45-61).
  • The Patented Solution: The patent describes creating prodrugs of treprostinil by chemically modifying its structure, such as by forming esters. These prodrugs are designed to be converted back into the active treprostinil compound within the body after administration, thereby providing a potential pathway for improved oral delivery (’908 Patent, Abstract; col. 5:6-14).
  • Technical Importance: The invention aims to provide an orally available form of a drug primarily limited to injection, which could significantly improve patient convenience and compliance for a chronic therapy (’908 Patent, col. 1:57-61).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶64).
  • Independent Claim 1 is a method of treatment claim comprising the following elements:
    • A method of treating pulmonary hypertension
    • Intravenously administering to a human suffering from pulmonary hypertension a formulation
    • The formulation comprises a therapeutically effective amount of treprostinil or a pharmaceutically acceptable salt or ester thereof
    • The formulation also comprises a diluent selected from the group consisting of sterile water, isotonic aqueous saline solution, and 5% dextrose solution (’908 Patent, col. 66:19-31).
  • The complaint does not explicitly reserve the right to assert dependent claims for this patent.

U.S. Patent No. 7,999,007 - "Buffer solutions having selective bactericidal activity against gram negative bacteria and methods of using same"

  • Issued: August 16, 2011 (Compl. ¶23).

Technology Synopsis

The patent addresses the risk of microbial contamination, particularly by gram-negative bacteria, in pharmaceutical solutions prepared for intravenous administration (’007 Patent, col. 1:21-43). The invention is a buffer solution with a high pH (greater than 10) and low buffer capacity that is claimed to selectively kill gram-negative bacteria while only inhibiting the growth of gram-positive bacteria, thereby reducing the risk of bloodstream infections associated with IV drug delivery (’007 Patent, Abstract).

Asserted Claims

At least claim 22 (Compl. ¶75).

Accused Features

Par's ANDA Products are alleged to be covered by one or more claims of the patent, suggesting the formulation of the generic drug will meet the composition limitations of the asserted claims (Compl. ¶75).

U.S. Patent No. 8,653,137 - "Buffer solutions having selective bactericidal activity against gram negative bacteria and methods of using same"

  • Issued: February 18, 2014 (Compl. ¶25).

Technology Synopsis

This patent is from the same family as the ’007 Patent and describes the same technology: a high-pH, low-capacity buffer with selective bactericidal activity against gram-negative bacteria (’137 Patent, Abstract).

Asserted Claims

At least claim 1 (Compl. ¶86).

Accused Features

The use of Par's ANDA Products, according to a label alleged to be the same or similar to that of REMODULIN®, is alleged to meet the limitations of the asserted method claims (Compl. ¶86).

U.S. Patent No. 8,658,694 - "Buffer solutions having selective bactericidal activity against gram negative bacteria and methods of using same"

  • Issued: February 25, 2014 (Compl. ¶27).

Technology Synopsis

This patent is from the same family as the ’007 and ’137 Patents and describes the same technology: a high-pH, low-capacity buffer with selective bactericidal activity against gram-negative bacteria (’694 Patent, Abstract).

Asserted Claims

At least claim 1 (Compl. ¶97).

Accused Features

The use of Par's ANDA Products, according to a label alleged to be the same or similar to that of REMODULIN®, is alleged to meet the limitations of the asserted method claims (Compl. ¶97).

III. The Accused Instrumentality

Product Identification

  • Par's generic versions of REMODULIN® (Treprostinil Sodium) Injection, submitted to the FDA under ANDA No. 209382 (Compl. ¶30).

Functionality and Market Context

  • The accused products are generic versions of UTC's injectable drug REMODULIN® and contain the same active pharmaceutical ingredient, treprostinil sodium (Compl. ¶37). The ANDA seeks approval to market the products for the same indication: the treatment of pulmonary arterial hypertension (Compl. ¶38). The complaint alleges that Par has represented to the FDA that its products are bioequivalent to REMODULIN® and that the proposed labeling is substantially the same as the approved labeling for REMODULIN® (Compl. ¶¶39, 41).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a claim-chart analysis of the ’393 Patent. The complaint makes a conclusory allegation that "Par's ANDA Products or an intermediate in their manufacture is covered by one or more claims of the '393 patent" without mapping any aspect of the accused product or its alleged manufacturing process to the specific steps of the asserted product-by-process claims (Compl. ¶53).

’908 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating pulmonary hypertension Defendant's ANDA product is indicated for the treatment of pulmonary arterial hypertension. ¶38 col. 66:19-20
comprising intravenously administering to a human suffering from pulmonary hypertension a formulation The proposed product label allegedly instructs patients and healthcare providers to administer the product intravenously. ¶65 col. 66:20-22
comprising a therapeutically effective amount of treprostinil or a pharmaceutically acceptable salt or ester thereof The ANDA product contains treprostinil sodium as its active pharmaceutical ingredient. ¶37 col. 66:22-25
and a diluent selected from the group consisting of sterile water, isotonic aqueous saline solution, and 5% dextrose solution. The proposed product label allegedly instructs users to dilute the product in a diluent prior to intravenous administration. ¶65 col. 66:25-28

Identified Points of Contention

  • Scope Questions (’393 Patent): The primary point of contention regarding the ’393 Patent is its validity. The subsequent cancellation of all claims in IPR proceedings, though occurring after the complaint was filed, suggests that the patentability of the claimed process was a central issue for dispute.
  • Technical and Legal Questions (’908 Patent): The infringement theory for this method claim is one of inducement. A key question will be whether the specific instructions on Defendant's final, FDA-approved label will direct users to perform every step of the claimed method, thereby directly infringing the claim. The definition of "formulation" may also be contested, raising the question of whether Par's drug product combined with a separate diluent (as instructed by the label) constitutes the claimed "formulation" that is administered.

V. Key Claim Terms for Construction

The subsequent cancellation of all asserted claims of the ’393 Patent in IPR proceedings may render a detailed claim construction analysis for its terms moot. For the ’908 Patent, practitioners may focus on the following term:

  • The Term: "formulation"
  • Context and Importance: This term is critical because the act of infringement is the "administering [of] a formulation." The complaint alleges that users will be induced to create this formulation by combining Defendant's drug product with a diluent as instructed on the label (Compl. ¶65). Defendant may argue that it only sells one component (the treprostinil solution) and not the final, complete "formulation" as required by the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification may describe the invention in terms of a kit or system where the active drug is intended to be combined with a diluent before administration, which could support an interpretation where the "formulation" encompasses the drug as supplied for its intended use.
    • Evidence for a Narrower Interpretation: The patent may consistently use the term "formulation" to refer to the final, ready-to-inject solution. Defendant could argue that because it does not make, use, or sell this final mixture, it cannot be liable for direct infringement, which would raise the bar for proving inducement.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement for the ’908, ’007, ’137, and ’694 patents. The basis for these allegations is that Defendant's proposed product labeling will actively instruct and encourage patients and healthcare providers to use the generic product in a manner that directly infringes the asserted method claims (Compl. ¶¶65, 76, 87, 98). The complaint also alleges contributory infringement, stating the product has no substantial non-infringing uses (Compl. ¶¶66, 77, 88, 99).
  • Willful Infringement: The complaint seeks a declaration that this is an "exceptional case" under 35 U.S.C. § 285 (Compl. ¶¶58, 68, 79, 90, 101). This allegation is based on Defendant's alleged pre-suit knowledge of the patents, as evidenced by its ANDA submission and Paragraph IV notice letter, and the allegation that Defendant "acted without a reasonable basis for believing that it would not be liable for infringement" (Compl. ¶58).

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

  1. Patent Viability: A threshold issue is the viability of the asserted patents. The post-filing cancellation of all claims of the ’393 patent in an Inter Partes Review will likely be dispositive for that portion of the case. The validity of the remaining formulation and method patents will be a central battleground.
  2. Scope of Induced Infringement: For the asserted method claims, the case will likely turn on the doctrine of inducement. A key evidentiary question will be whether the specific language of Defendant’s final, FDA-approved label instructs users to perform acts that map onto every limitation of the asserted claims, thereby inducing direct infringement.
  3. Construction of "Formulation": The outcome for several claims may depend on claim construction, specifically whether the term "formulation" can be construed to read on a system where the Defendant provides one component (the drug concentrate) and instructs the user to combine it with another (a diluent).