DCT

1:24-cv-01105

Galderma Laboratories LP v. Macleods Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:24-cv-01105, D. Del., 10/04/2024
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Macleods Pharma USA, Inc. is a Delaware corporation and both defendants are subject to personal jurisdiction in the state, partly based on their history of regularly engaging in patent litigation in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic 40 mg doxycycline capsule constitutes an act of infringement of two patents related to once-daily, low-dose tetracycline formulations.
  • Technical Context: The technology concerns pharmaceutical formulations designed to deliver a low, sub-antimicrobial dose of the antibiotic doxycycline to treat chronic inflammatory conditions like rosacea, while avoiding antibiotic side effects and improving patient compliance.
  • Key Procedural History: The patents-in-suit are listed in the FDA's "Orange Book" for Plaintiff's ORACEA® product. Defendant notified Plaintiff of its ANDA filing and Paragraph IV certification via a letter dated August 21, 2024. This suit was filed within the statutory 45-day window. Notably, the claims of U.S. Patent No. 8,206,740 survived an inter partes review (IPR) proceeding (IPR2013-00368), a fact which may influence subsequent validity challenges.

Case Timeline

Date Event
2003-04-07 Priority Date for ’532 and ’740 Patents
2010-07-06 U.S. Patent No. 7,749,532 Issues
2012-06-26 U.S. Patent No. 8,206,740 Issues
2013-06-20 IPR Petition Filed Against ’740 Patent
2015-05-13 IPR Final Written Decision Upholds Asserted Claims of ’740 Patent
2024-08-21 Defendant Sends Paragraph IV Notice Letter to Plaintiff
2024-10-04 Complaint for Patent Infringement Filed

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

U.S. Patent No. 7,749,532 - Once Daily Formulations of Tetracyclines (issued Jul. 6, 2010)

The Invention Explained

  • Problem Addressed: The patent describes two primary problems with conventional doxycycline therapy: (1) higher, antibiotic-level doses can lead to undesirable side effects, including the elimination of healthy intestinal flora and the development of antibiotic-resistant organisms; and (2) therapies requiring multiple daily doses, such as the twice-daily Periostat® product, present patient compliance challenges (’532 Patent, col. 2:1-17).
  • The Patented Solution: The invention is a once-daily oral formulation of doxycycline that delivers a total dose of less than 50 mg (preferably 40 mg). It combines an immediate-release (IR) component and a delayed-release (DR) component to achieve steady-state blood levels within a specific therapeutic window—high enough to inhibit collagenase for anti-inflammatory effects, but low enough to avoid antibacterial activity (’532 Patent, col. 2:21-41; col. 2:46-59). This design aims to provide therapeutic benefits for conditions like rosacea with the convenience of a single daily dose and reduced side effects.
  • Technical Importance: The formulation provides a method to decouple doxycycline's anti-inflammatory properties from its antibiotic properties, enabling its long-term use for chronic conditions while improving patient adherence through a simplified dosing schedule (’532 Patent, col. 2:1-9).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶31).
  • Claim 1 requires:
    • An oral pharmaceutical composition of doxycycline.
    • Which at a once-daily dosage provides steady state blood levels between 0.1 µg/ml and 1.0 µg/ml.
    • The composition consists of:
      • An immediate release (IR) portion with about 30 mg of doxycycline.
      • A delayed release (DR) portion with about 10 mg of doxycycline, where the DR portion is in the form of "pellets coated with at least one enteric polymer."
      • One or more pharmaceutically acceptable excipients.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 8,206,740 - Once Daily Formulations of Tetracyclines (issued Jun. 26, 2012)

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’532 patent, the ’740 patent addresses the same problems of patient compliance and side effects associated with traditional doxycycline regimens (’740 Patent, col. 2:1-17).
  • The Patented Solution: The invention is likewise a once-daily, low-dose (40 mg) doxycycline formulation with IR and DR components designed to maintain blood concentrations in a sub-antimicrobial, anti-inflammatory range (’740 Patent, col. 2:21-43). The core inventive concept is identical to that of its parent patent.
  • Technical Importance: The technology provides an alternative means of achieving the therapeutic goals described in the ’532 patent, potentially through a broader range of formulation technologies (’740 Patent, col. 2:1-9).

Key Claims at a Glance

  • The complaint asserts at least independent claim 1 (Compl. ¶31).
  • Claim 1 requires:
    • An oral pharmaceutical composition of doxycycline.
    • Which at a once-daily dosage provides steady state blood levels between 0.1 µg/ml and 1.0 µg/ml.
    • The composition consists of:
      • An immediate release (IR) portion with 30 mg of doxycycline.
      • A delayed release (DR) portion with 10 mg of doxycycline.
      • Optionally, one or more pharmaceutically acceptable excipients.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

Defendant's proposed generic "Doxycycline Capsules, 40 mg," which is the subject of Abbreviated New Drug Application (ANDA) No. 210381 (Compl. ¶9).

Functionality and Market Context

The complaint alleges that the accused ANDA product is a generic version of Plaintiff's ORACEA® Capsules and that Defendant has submitted data to the FDA intended to demonstrate its bioequivalence to ORACEA® (Compl. ¶31). This implies the accused product is a 40 mg capsule formulated to be absorbed and metabolized in a manner that produces a pharmacokinetic profile equivalent to the brand-name drug, which is the commercial embodiment of the patented inventions (Compl. ¶24).

IV. Analysis of Infringement Allegations

The complaint alleges infringement based on Defendant's filing of its ANDA, asserting that the product described therein will meet all limitations of at least claim 1 of each patent-in-suit (Compl. ¶31). No probative visual evidence provided in complaint.

’532 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An oral pharmaceutical composition of doxycycline, which at a once-daily dosage will give steady state blood levels of doxycycline of a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml The accused ANDA product is a 40 mg doxycycline capsule that is alleged to be bioequivalent to ORACEA®, and is therefore designed to achieve this pharmacokinetic profile. ¶31 col. 2:38-41
(i) an immediate release (IR) portion comprising a drug, wherein the drug consists of about 30 mg doxycycline The accused 40 mg doxycycline capsule is alleged to contain an immediate-release component comprising approximately 30 mg of doxycycline. ¶31 col. 2:54-59
(ii) a delayed release (DR) portion comprising a drug, wherein the drug consists of about 10 mg doxycycline, in which the DR portion is in the form of pellets coated with at least one enteric polymer The accused 40 mg doxycycline capsule is alleged to contain a delayed-release component comprising approximately 10 mg of doxycycline as enteric-coated pellets. ¶31 col. 7:12-16
(iii) one or more pharmaceutically acceptable excipients The accused ANDA product is alleged to contain pharmaceutically acceptable excipients necessary for its formulation. ¶31 col. 4:5-14

’740 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An oral pharmaceutical composition of doxycycline, which at a once-daily dosage will give steady state blood levels of doxycycline of a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml The accused ANDA product is a 40 mg doxycycline capsule that is alleged to be bioequivalent to ORACEA®, and is therefore designed to achieve this pharmacokinetic profile. ¶31 col. 2:40-43
(i) an immediate release (IR) portion comprising 30 mg doxycycline The accused 40 mg doxycycline capsule is alleged to contain an immediate-release component comprising 30 mg of doxycycline. ¶31 col. 11:60-61
(ii) a delayed release (DR) portion comprising 10 mg doxycycline The accused 40 mg doxycycline capsule is alleged to contain a delayed-release component comprising 10 mg of doxycycline. ¶31 col. 11:62-63

Identified Points of Contention

  • Scope Questions: A central question for the ’740 patent will be the scope of a "delayed release (DR) portion." As this claim is not limited to the "enteric-coated pellets" of the ’532 patent, a dispute may arise over whether Defendant's chosen DR technology, if different, still falls within this broader definition. Another question may concern the scope of "about 30 mg" and "about 10 mg" in the ’532 patent claims.
  • Technical Questions: The primary technical question is whether the specific formulation detailed in Defendant's confidential ANDA actually contains the elements required by the claims. For the ’532 patent, does the accused product utilize "pellets coated with at least one enteric polymer" for its delayed-release component? Discovery into the ANDA's contents will be necessary to resolve this.

V. Key Claim Terms for Construction

  • The Term: "a delayed release (DR) portion" (’740 Patent, Claim 1)

    • Context and Importance: This term's construction is critical because it defines the scope of the ’740 patent's protection for the delayed-release element. Unlike the narrower claim in the ’532 patent, it is not textually limited to a specific mechanism like enteric-coated pellets. Practitioners may focus on this term to determine if a generic formulation using an alternative DR technology (e.g., a matrix tablet) would infringe.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification discusses multiple ways to formulate drug products, including tablets with a "tablet matrix, which rapidly disperses the particles after ingestion," suggesting that mechanisms other than coated pellets were contemplated (’740 Patent, col. 8:27-30).
      • Evidence for a Narrower Interpretation: The patent's preferred embodiment and all detailed examples describe the DR portion as enteric-coated pellets designed for pH-triggered release in the intestine (’740 Patent, Example 2, col. 9:48-67). A party could argue the claims should be limited to what the inventors actually described as their invention.

  • The Term: "steady state blood levels of doxycycline of a minimum of 0.1 µg/ml and a maximum of 1.0 µg/ml" (’532 and ’740 Patents, Claim 1)

    • Context and Importance: This pharmacokinetic (PK) limitation is a cornerstone of the invention, defining the sub-antimicrobial therapeutic window. Its construction will be central to determining infringement, as it depends on how blood levels are measured and interpreted.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party may argue this refers to an average concentration achieved across a general patient population under typical use, rather than a rigid requirement for every individual. The patent's summary describes this as a general goal of the formulation (’532 Patent, col. 2:38-41).
      • Evidence for a Narrower Interpretation: The specification provides detailed PK data, including graphs of mean plasma concentrations from a human clinical study (e.g., ’532 Patent, Figs. 5-6; Table 1). A party could argue that the claim should be construed in light of these specific results, potentially requiring the accused product to match these profiles under similar testing conditions.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that if Defendant commercially markets its ANDA product, it will induce infringement by others (e.g., patients) and contribute to infringement by, for example, providing instructions for use that mirror the patented method (Compl. ¶34).
  • Willful Infringement: Willfulness is alleged based on Defendant having had pre-suit knowledge of the patents-in-suit before filing its ANDA (Compl. ¶37). The sending of the Paragraph IV certification letter (Compl. ¶26) provides further evidence of knowledge.

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

  1. A central issue will be one of formulation equivalence: Will discovery into the confidential ANDA reveal that Defendant's delayed-release mechanism is the specific "enteric-coated pellets" recited in the ’532 patent, or does it employ a different technology? If the latter, the case will turn on whether that alternative technology falls within the broader scope of a "delayed release portion" as claimed in the ’740 patent.
  2. The case presents a key question of validity resilience: The claims of the ’740 patent were previously confirmed as patentable in an inter partes review. A significant issue will be whether Defendant can present new prior art or arguments sufficient to overcome this earlier finding, and how much deference the court will give to the Patent Trial and Appeal Board's prior validity determination.
  3. A critical evidentiary question will be one of pharmacokinetic proof: The dispute may hinge on a battle of experts regarding whether Defendant's product is proven to achieve the specific "steady state blood levels" required by the claims. This will involve interpreting clinical data and debating the proper methodology for demonstrating bioequivalence for the purposes of infringement.