DCT

1:22-cv-01442

Pierre Fabre Medicament SAS v. Annora Pharma Pvt Ltd

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01442, D. Del., 11/02/2022
  • Venue Allegations: Venue is alleged to be proper because the defendant, Annora Pharma Private Limited, is a foreign corporation not residing in any U.S. state and may therefore be sued in any judicial district.
  • Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' HEMANGEOL® (propranolol hydrochloride) oral solution constitutes an act of patent infringement.
  • Technical Context: The technology involves the use of a beta-blocker, propranolol, for the systemic treatment of infantile hemangiomas, a common type of benign vascular tumor found in infants.
  • Key Procedural History: This action was triggered by Defendant’s September 19, 2022 notice letter to Plaintiffs, which stated that Defendant had submitted an ANDA to the FDA seeking approval to market a generic version of HEMANGEOL® prior to the expiration of the patents-in-suit. The asserted patents are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations (the "Orange Book").

Case Timeline

Date Event
2007-10-19 Earliest Priority Date for ’489 and ’262 Patents
2012-12-25 U.S. Patent No. 8,338,489 Issue Date
2015-03-24 U.S. Patent No. 8,987,262 Issue Date
2022-09-19 Defendant's ANDA Notice Letter to Plaintiffs
2022-11-02 Complaint Filing Date

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

U.S. Patent No. 8,338,489 - Use of a Beta Blocker for the Manufacture of a Medicament for the Treatment of Hemangiomas

  • Issued: December 25, 2012

The Invention Explained

  • Problem Addressed: The patent describes infantile hemangiomas (IH) as the most common soft tissue tumors of infancy ('489 Patent, col. 1:30-32). It notes that prior first-line treatments, such as systemic corticosteroids, have limited response rates (30-60%) and can cause significant adverse effects, including "cushingoid facies, irritability, [and] growth suppression" ('489 Patent, col. 2:56-68). Other options like interferon alfa carry a risk of neurotoxicity in young children ('489 Patent, col. 3:1-4).
  • The Patented Solution: The invention is the use of a beta-blocker, specifically propranolol, to treat hemangiomas ('489 Patent, Abstract). The patent discloses that propranolol, a well-tolerated drug used for cardiologic indications in children, was unexpectedly found to be "very efficient to control the growth of IH and even to treat IH" ('489 Patent, col. 3:33-35). The proposed mechanisms of action include inducing vasoconstriction and triggering apoptosis in the tumor's capillary endothelial cells ('489 Patent, col. 6:11-28).
  • Technical Importance: The invention provided a new therapeutic option for a common pediatric condition that offered a potentially more effective and safer alternative to the existing standard of care ('489 Patent, col. 3:13-18).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶40).
  • Claim 1 of the '489 Patent recites:
    • A method for treating a hemangioma
    • comprising administering a medicament comprising a beta blocker which is propranolol or a pharmaceutically acceptable salt thereof
    • wherein the medicament is administered at a daily dose of less than or equal to 5 mg/kg of body weight of the patient.

U.S. Patent No. 8,987,262 - Use of a Beta Blocker for the Manufacture of a Medicament for the Treatment of Hemangiomas

  • Issued: March 24, 2015

The Invention Explained

  • Problem Addressed: As a continuation-in-part of the application leading to the '489 patent, the '262 Patent addresses the same technical problem: the need for safer and more effective treatments for infantile hemangiomas compared to the then-standard options like corticosteroids and interferon, which had significant side effects and/or limited efficacy ('262 Patent, col. 2:58-col. 3:12).
  • The Patented Solution: The patent describes a method of treating capillary or infantile hemangiomas by administering an "efficient dose of a beta blocker" ('262 Patent, Claim 1). The specification, similar to the parent '489 Patent, explains that propranolol is a preferred beta-blocker and describes its unexpected efficacy in causing regression of these tumors, providing experimental examples in infants ('262 Patent, col. 3:23-25; col. 8:53-col. 10:55).
  • Technical Importance: This patent family documents the repurposing of a known cardiovascular drug to establish a new treatment paradigm for a common benign tumor in infants, shifting away from less effective and more toxic therapies ('262 Patent, col. 3:16-21).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶48).
  • Claim 1 of the '262 Patent recites:
    • A method for treating a patient having a capillary or infantile hemangioma,
    • comprising administering to the patient a pharmaceutically acceptable and efficient dose of a beta blocker.
  • Dependent claims further specify the beta-blocker as non-selective (Claim 3), propranolol (Claim 4), or acebutolol (Claim 9), and define dosage ranges (Claim 17).

III. The Accused Instrumentality

Product Identification

Defendant Annora’s Abbreviated New Drug Application (“ANDA”) No. 217567 product, which is a generic version of Pierre Fabre’s HEMANGEOL® (Propranolol Hydrochloride) Solution, Oral, 4.28 MG/ML (Compl. ¶¶1-2).

Functionality and Market Context

The accused instrumentality is a proposed generic drug product. By submitting its ANDA, Annora has represented to the FDA that its product contains the same active ingredient (propranolol hydrochloride), has the same route of administration, dosage form, strength, and is intended for the same use as the reference listed drug, HEMANGEOL® (Compl. ¶35). The complaint alleges that HEMANGEOL® is the only FDA-approved systemic therapy for infantile hemangioma, and that Annora intends to launch its generic product upon FDA approval, prior to the expiration of the Asserted Patents (Compl. ¶¶17, 33).

Visual Evidence

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'489 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating a hemangioma Defendant's ANDA Product is a generic version of HEMANGEOL®, a drug for the treatment of infantile hemangioma, and seeks approval for that same use. ¶1, ¶35 col. 3:41-43
comprising administering a medicament comprising a beta blocker which is propranolol or a pharmaceutically acceptable salt thereof Defendant's ANDA Product contains propranolol hydrochloride, which is a salt of the beta-blocker propranolol. ¶1, ¶35 col. 4:5-8
wherein the medicament is administered at a daily dose of less than or equal to 5 mg/kg of body weight of the patient. Defendant's ANDA Product is alleged to have the same use and strength as HEMANGEOL®, which implies that its proposed label will instruct administration at a dose that meets this limitation. ¶35 col. 5:40-44

'262 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating a patient having a capillary or infantile hemangioma, Defendant's ANDA seeks approval to market a generic version of HEMANGEOL®, a drug indicated for the treatment of infantile hemangioma. ¶1, ¶35 col. 3:43-45
comprising administering to the patient a pharmaceutically acceptable and efficient dose of a beta blocker. Defendant's ANDA Product contains propranolol, which is a beta-blocker (specified in dependent claim 4). The proposed label will instruct administration of what is represented to be an "efficient dose." ¶1, ¶35, ¶48 col. 3:45-49

Identified Points of Contention

  • Scope Questions: In this ANDA litigation, the infringement analysis under 35 U.S.C. § 271(e)(2) will focus on whether the use for which the defendant seeks approval falls within the scope of the patent claims. A key question for the court will be whether Annora's proposed product label will instruct administration in a manner that directly reads on every limitation of the asserted claims.
  • Technical Questions: Given that the accused product is a generic version of the plaintiffs' own product, a significant dispute over the technical operation (i.e., whether propranolol is a beta-blocker or whether it treats hemangiomas) appears unlikely. The central conflict will likely revolve around the validity of the patents, rather than non-infringement.

V. Key Claim Terms for Construction

"treating" ('489 Patent, Claim 1; '262 Patent, Claim 1)

  • Context and Importance: The definition of "treating" is fundamental to the scope of these method claims. Practitioners may focus on this term because its construction determines whether the method must result in a complete cure or if it also covers arresting tumor growth or causing partial regression.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification suggests "treating" includes managing the condition, stating that beta-blockers "may be very efficient to control the growth of IH and even to treat IH" ('489 Patent, col. 3:33-35), which could support a construction that does not require complete resolution.
    • Evidence for a Narrower Interpretation: The patent also describes more definitive outcomes, such as when a hemangioma becomes "completely flat" or undergoes "progressive improvement" ('489 Patent, col. 6:35-36; col. 7:52-53). A defendant might argue these examples limit "treating" to methods that achieve substantial or complete regression.

"efficient dose" ('262 Patent, Claim 1)

  • Context and Importance: This term in the independent claim of the '262 Patent is not defined by a specific numerical range, unlike the corresponding claim in the '489 Patent. Its construction is critical because it defines the dosage required for infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides examples of various dosages, including a range of "about 1 to 10 mg/kg of body weight of the patient" ('262 Patent, col. 6:59-60), suggesting "efficient" is any dose within a wide therapeutic window that produces a positive result.
    • Evidence for a Narrower Interpretation: The detailed examples in the specification describe successful treatment using specific doses, such as "2 mg/kg/day" or "3 mg/kg/day" ('262 Patent, col. 10:4-5, 40-41). A party could argue these specific embodiments narrow the meaning of an "efficient dose" to the ranges proven effective in the patent's own experiments.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval of its ANDA, Annora will induce infringement by causing third parties (e.g., physicians and patients) to use the accused product in an infringing manner. This inducement is allegedly based on the instructions for use that will be included in the product's labeling (Compl. ¶¶42, 50). The complaint also alleges contributory infringement, stating the product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶¶43, 51).
  • Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. However, it does request a finding that the case is "exceptional" and an award of reasonable attorneys' fees (Compl. Prayer for Relief ¶f).

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

This case presents a classic Hatch-Waxman dispute where the primary conflict is unlikely to be over infringement, but rather over the validity of the asserted patents. The key questions for the court will likely be:

  • A central question will be one of patentability, specifically obviousness: Given that propranolol was a known beta-blocker with a history of use in pediatric cardiology, was it obvious at the time of the invention to use it for the treatment of infantile hemangiomas? The outcome may depend on the court's analysis of the motivation to combine prior art references and the existence of a reasonable expectation of success.
  • A secondary issue may be one of claim scope: Does the term "efficient dose" in the '262 Patent, which is not numerically limited in the independent claim, render the claim indefinite, or is it sufficiently defined by the specification to inform a person of ordinary skill in the art of its scope?
  • Finally, an evidentiary question will concern the scope of the proposed label: Will the final, FDA-approved label for Annora's product contain instructions that fall squarely within all limitations of the asserted claims, thereby establishing direct evidence for induced infringement?