DCT

1:18-cv-01014

Horizon Medicines LLC v. Alkem Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01014, D. Del., 07/09/2018
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware based on Defendant’s prior consent to jurisdiction in the district, its systematic and continuous contacts with the state through the marketing and sales of other generic drugs, and its intent to market and sell the accused product in Delaware upon approval.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s DUEXIS® pharmaceutical product constitutes an act of infringement of six patents covering the product’s composition and methods of use.
  • Technical Context: The technology concerns a combination drug product that pairs ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), with famotidine, a stomach acid-reducing agent, to mitigate the risk of gastrointestinal ulcers commonly associated with NSAID use.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff’s receipt of a notification letter from Defendant, dated May 29, 2018. This letter contained a Paragraph IV certification stating Defendant’s belief that Plaintiff’s patents are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2007-01-24 ’451 Patent Priority Date
2007-11-30 ’033, ’127, ’202, ’910, ’228 Patents Priority Date
2011-11-29 U.S. Patent 8,067,033 Issued
2011-11-29 U.S. Patent 8,067,451 Issued
2012-11-13 U.S. Patent 8,309,127 Issued
2012-11-27 U.S. Patent 8,318,202 Issued
2013-05-28 U.S. Patent 8,449,910 Issued
2013-08-06 U.S. Patent 8,501,228 Issued
2018-05-29 Plaintiff receives Defendant’s ANDA notification letter
2018-07-09 Complaint Filing Date

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

U.S. Patent No. 8,067,033 - "Stable Compositions of Famotidine and Ibuprofen"

  • Issued: November 29, 2011

The Invention Explained

  • Problem Addressed: The patent describes the technical challenge that while combining the NSAID ibuprofen with the H2-receptor antagonist famotidine can reduce the risk of gastrointestinal ulcers, the two active ingredients are chemically incompatible, complicating the creation of a stable, single-unit dosage form. ('033 Patent, col. 1:45-50).
  • The Patented Solution: The invention is a pharmaceutical composition, such as a 'tablet-in-tablet' formulation, where a core containing famotidine is surrounded by a portion containing ibuprofen. This structure improves stability by controlling and minimizing the surface area over which the two incompatible drugs are in direct physical contact. ('033 Patent, Abstract; col. 2:1-9).
  • Technical Importance: This formulation strategy enables the creation of a stable, single-pill combination therapy that can improve patient compliance over regimens requiring two separate pills, thereby enhancing the prophylactic effect against NSAID-induced ulcers. ('033 Patent, col. 1:40-44).

Key Claims at a Glance

  • The complaint does not identify specific asserted claims, alleging infringement of "one or more claims." (Compl., Prayer for Relief ¶A). Claim 1 is the first independent claim.
  • Essential elements of Independent Claim 1 include:
    • A pharmaceutical composition comprising a first portion with 800 mg ibuprofen and a second portion with 26.6 mg famotidine.
    • The surface area of direct physical contact between the ibuprofen and famotidine does not exceed 130 mm².
    • The composition is stable, with no more than about 1% sulfamide present after one month at 40° C. and 75% relative humidity.
    • The composition is formulated for rapid, simultaneous release of both drugs and is not enterically coated or formulated for sustained/delayed release.
    • The composition is for use according to a three-times-per-day (TID) administration schedule.

U.S. Patent No. 8,067,451 - "Methods and Medicaments for Administration of Ibuprofen"

  • Issued: November 29, 2011

The Invention Explained

  • Problem Addressed: The patent background explains that while cotherapy with NSAIDs and famotidine can reduce ulcer risk, existing therapies are not widely used and more effective methods are needed to improve patient outcomes and protection against gastric side effects. ('451 Patent, col. 3:56-62).
  • The Patented Solution: The patent claims a method of administering ibuprofen and famotidine on a three-times-per-day (TID) schedule. Based on pharmacokinetic modeling, the patent asserts that this TID regimen provides a superior therapeutic effect—specifically, maintaining a higher intragastric pH for a greater portion of the day—compared to a conventional twice-a-day (BID) administration of the same total daily dose of famotidine. ('451 Patent, Abstract; col. 10:9-16).
  • Technical Importance: The invention proposes that a specific dosing frequency (TID) provides superior gastric protection and reduces interpatient variability compared to standard BID dosing, thereby decreasing the likelihood that a patient will experience dangerously low gastric pH levels during NSAID treatment. ('451 Patent, col. 10:26-36).

Key Claims at a Glance

  • The complaint does not identify specific asserted claims, alleging infringement of "one or more claims." (Compl., Prayer for Relief ¶B). Claim 1 is the first independent claim.
  • Essential elements of Independent Claim 1 include:
    • A method for administering ibuprofen to a subject.
    • The method involves administering a first, second, and third dose of an oral dosage form within a 24-hour cycle.
    • Each dosage form contains from 775 mg to 825 mg of ibuprofen and from 25 mg to 28 mg of famotidine.
    • The drugs are formulated for immediate release.

U.S. Patent No. 8,309,127 - "Stable Compositions of Famotidine and Ibuprofen"

  • Patent Identification: U.S. Patent No. 8,309,127, issued November 13, 2012. (Compl. ¶ 17).
  • Technology Synopsis: This patent, like the ’033 Patent, addresses the chemical incompatibility between ibuprofen and famotidine. It claims a pharmaceutical composition that manages this incompatibility to ensure stability, for example by controlling the physical arrangement of the two active ingredients. (Compl. ¶ 18; '127 Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl., Prayer for Relief ¶C).
  • Accused Features: The Defendant's generic ibuprofen and famotidine tablets, which are alleged to be covered by the patent. (Compl. ¶¶ 55-56).

U.S. Patent No. 8,318,202 - "Stable Compositions of Famotidine and Ibuprofen"

  • Patent Identification: U.S. Patent No. 8,318,202, issued November 27, 2012. (Compl. ¶ 19).
  • Technology Synopsis: This patent is part of the same family as the ’033 and ’127 patents, claiming stable pharmaceutical compositions of the chemically incompatible drugs ibuprofen and famotidine. The claimed invention achieves stability through specific formulation characteristics. (Compl. ¶ 20; '202 Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl., Prayer for Relief ¶D).
  • Accused Features: The Defendant's generic ibuprofen and famotidine tablets. (Compl. ¶¶ 65-66).

U.S. Patent No. 8,449,910 - "Stable Compositions of Famotidine and Ibuprofen"

  • Patent Identification: U.S. Patent No. 8,449,910, issued May 28, 2013. (Compl. ¶ 21).
  • Technology Synopsis: This patent continues the same theme as the other composition patents, claiming stable formulations of ibuprofen and famotidine. The claims are directed to compositions that overcome the chemical incompatibility of the active ingredients to provide a stable, single-unit dosage form. (Compl. ¶ 22; '910 Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl., Prayer for Relief ¶E).
  • Accused Features: The Defendant's generic ibuprofen and famotidine tablets. (Compl. ¶¶ 75-76).

U.S. Patent No. 8,501,228 - "Stable Compositions of Famotidine and Ibuprofen"

  • Patent Identification: U.S. Patent No. 8,501,228, issued August 6, 2013. (Compl. ¶ 23).
  • Technology Synopsis: This patent also claims stable pharmaceutical compositions of ibuprofen and famotidine. Like its family members, it describes and claims formulations designed to prevent the degradation that occurs when the two active ingredients are in direct contact. (Compl. ¶ 24; '228 Patent, Abstract).
  • Asserted Claims: "one or more claims" (Compl., Prayer for Relief ¶F).
  • Accused Features: The Defendant's generic ibuprofen and famotidine tablets. (Compl. ¶¶ 85-86).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendant Alkem's proposed generic version of DUEXIS®, identified as "ibuprofen and famotidine tablets, 800 mg/26.6 mg" ("the Alkem Product"). The act of infringement cited is the submission of Abbreviated New Drug Application (ANDA) No. 211890 to the FDA. (Compl. ¶¶ 1, 6, 29).
  • Functionality and Market Context: The complaint alleges that the Alkem Product is a generic drug intended to be bioequivalent to DUEXIS®. (Compl. ¶ 30). Its function is to provide relief for conditions such as rheumatoid arthritis and osteoarthritis while concurrently decreasing the risk of developing upper gastrointestinal ulcers in patients taking ibuprofen. (Compl. ¶ 29). Alkem allegedly intends to commercially manufacture, market, and sell the product throughout the United States upon receiving final FDA approval. (Compl. ¶¶ 6-7).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or specify which claims of the patents-in-suit are asserted. The infringement theory is based on 35 U.S.C. § 271(e)(2)(A), which defines the submission of an ANDA seeking approval to market a generic version of a patented drug as an act of infringement. The following summary is based on the allegations in the complaint and representative independent claims from the lead patents.

U.S. Patent No. 8,067,033 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a first portion that comprises 800 mg ibuprofen and a second portion that comprises 26.6 mg famotidine The Alkem Product is an ibuprofen and famotidine tablet with dosages of 800 mg and 26.6 mg, respectively. ¶29 col. 12:19-26
wherein the surface area of direct physical contact between ibuprofen and famotidine does not exceed 130 mm² The complaint alleges infringement without specifying the physical structure of the Alkem Product, asserting that the product is covered by the patent. ¶¶ 35, 36 col. 2:1-9
wherein no more than about 1% sulfamide is present when the composition is stored at 40° C. and 75% relative humidity for a period of one month The complaint alleges infringement, which presupposes the Alkem Product meets the claimed stability requirements. ¶¶ 35, 36 col. 4:55-64
wherein the composition is for use according to a TID (three times per day) administration schedule The Alkem ANDA seeks approval for the same indications and uses as DUEXIS®, which is prescribed for TID use. ¶29 col. 12:35-40

U.S. Patent No. 8,067,451 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for administration of ibuprofen...comprising: administering a first dose...a second dose...and administering a third dose...within a 24 hour dosing cycle The Alkem Product, if approved and commercialized, will be sold with a label instructing use for the same indications as DUEXIS®, which includes a three-times-per-day dosing regimen. ¶¶ 29, 47 col. 10:9-12
of an oral dosage form containing from 775 mg to 825 mg ibuprofen and from 25 mg to 28 mg famotidine The Alkem Product contains 800 mg of ibuprofen and 26.6 mg of famotidine, which falls within the claimed dosage ranges. ¶29 col. 2:1-11
where the ibuprofen and the famotidine are formulated for immediate release The complaint alleges infringement, which presupposes the Alkem Product is formulated for immediate release, consistent with its status as a bioequivalent generic of DUEXIS®. ¶¶ 30, 46 col. 2:14-17
  • Identified Points of Contention:
    • Structural Questions ('033 Patent family): A primary factual question for the composition patents will be whether Alkem’s proposed generic product employs the specific physical structure required by the claims, particularly the limitation on the surface area of direct contact between the active ingredients. The complaint does not detail the formulation of the Alkem Product, so it is an open question whether it uses a tablet-in-tablet design or an alternative formulation that may design around this structural limitation while maintaining bioequivalence.
    • Legal Questions ('451 Patent): For the method-of-use patent, a central legal question will likely concern validity, specifically obviousness. A point of contention may be whether it would have been obvious to a person of ordinary skill in the art that administering famotidine three times per day, rather than the conventional twice-daily schedule, would yield superior gastric protection when co-administered with ibuprofen.

V. Key Claim Terms for Construction

The complaint does not identify any claim terms for construction. Based on the technology, the following terms may become central to the dispute.

  • The Term: "direct physical contact over a surface area" ('033 Patent)

  • Context and Importance: This term is the central limitation of the composition claims, distinguishing the invention from a simple admixture of incompatible ingredients. The infringement analysis for the composition patents may depend entirely on whether the physical structure of the Alkem Product falls within the scope of this term.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent specification provides a specific mathematical formula for calculating the maximum permissible surface area: (25 mm²) + (3.75 mm² × x), where x is the mass of famotidine. ('033 Patent, col. 4:55-58). A party could argue this formula is the definitive and sole test for infringement, regardless of the specific physical arrangement (e.g., tablet-in-tablet vs. coated multiparticulates).
    • Evidence for a Narrower Interpretation: The detailed description heavily emphasizes a 'tablet-in-tablet' or 'core' and 'shell' structure as the embodiment of the invention. ('033 Patent, col. 4:46-54). A party could argue that the "surface area" limitation must be interpreted in the context of this specific structure, and that alternative formulations that lack a distinct core and shell do not meet the limitation, even if some incidental contact between ingredients occurs.

  • The Term: "administering... a first dose... a second dose... and a third dose... within a 24 hour dosing cycle" ('451 Patent)

  • Context and Importance: This phrase defines the temporal scope of the claimed method. Infringement of the '451 Patent requires performing these steps. The dispute will likely focus on whether this claimed method is valid (i.e., non-obvious) rather than on the meaning of the term itself.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The plain language suggests any three administrations within a 24-hour period.
    • Evidence for a Narrower Interpretation: The specification describes this as a 'TID (three-times-per-day) schedule,' which implies a regular, structured daily regimen rather than three arbitrary doses. ('451 Patent, col. 2:30-31). The patent's pharmacokinetic modeling is based on such a regular schedule. This context might be used to argue against an overly broad interpretation that covers irregular or accidental dosing patterns.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval and commercialization, Defendant will actively induce and contribute to the infringement of all six patents. (e.g., Compl. ¶¶ 37, 47). This is based on the allegation that Alkem will sell its product with instructions for use that direct physicians and patients to engage in infringing acts, such as administering the patented composition or performing the patented method of treatment.
  • Willful Infringement: Willfulness is alleged for all six patents. (e.g., Compl. ¶¶ 38, 48). The complaint asserts that Defendant had actual and constructive notice of the patents-in-suit as of their issue dates, and that the filing of the ANDA with a Paragraph IV certification constitutes pre-suit knowledge of the patents and the alleged infringement.

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

  • A core issue will be one of structural infringement vs. design-around: Does the Defendant’s proposed generic product, designed for bioequivalence, adopt the specific tablet-in-tablet structure with a minimized contact surface area as claimed in the composition patents (e.g., the ’033 Patent), or does it achieve the required stability and bioequivalence through a technically different, non-infringing formulation?
  • A central validity question will be one of obviousness: Was the discovery that a three-times-daily (TID) dosing regimen for famotidine provides superior gastric protection compared to a twice-daily (BID) regimen when co-administered with ibuprofen—as claimed in the ’451 Patent—an inventive step, or would it have been obvious to a person of ordinary skill in pharmaceutical sciences at the time?
  • A key evidentiary question will concern chemical incompatibility and stability: The patents-in-suit are premised on solving the problem of chemical incompatibility. The infringement and validity analyses may turn on evidence presented by both parties regarding the degree of this incompatibility and whether the specific structural or methodological solutions claimed in the patents were necessary and non-obvious ways to create a stable and effective combination product.