DCT

3:18-cv-11218

Amgen Inc v. Emcure Pharma Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:18-cv-11218, D.N.J., 06/28/2018
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Heritage Pharmaceuticals has its principal place of business in the district, and Defendant Emcure Pharmaceuticals is a foreign corporation.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market generic versions of the drug OTEZLA® (apremilast) constitutes an act of infringement of two U.S. patents covering the drug's active compound and its method of use for treating psoriatic arthritis.
  • Technical Context: The technology involves a stereomerically pure pharmaceutical compound, apremilast, which is an inhibitor of phosphodiesterase 4 (PDE4) used in treatments for inflammatory conditions.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 211681 and a corresponding Paragraph IV Certification notice letter to Plaintiff on May 25, 2018. Plaintiff filed this complaint within the statutory 45-day window. Plaintiff's product, OTEZLA®, was approved by the FDA on March 21, 2014, and received a five-year new chemical entity regulatory exclusivity period expiring March 21, 2019.

Case Timeline

Date Event
2002-03-20 ’638 Patent Priority Date
2008-09-23 ’638 Patent Issue Date
2013-03-14 ’854 Patent Priority Date
2014-03-21 OTEZLA® (apremilast) FDA Approval
2018-01-23 ’854 Patent Issue Date
2018-05-25 Paragraph IV Notice Letter Received
2018-06-28 Complaint Filing Date

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

U.S. Patent No. 7,427,638

  • Patent Identification: U.S. Patent No. 7,427,638, titled "(+)-2-[1-(3-Ethoxy-4-Methoxyphenyl)-2-Methylsulfonylethyl]-4-Acetylaminoisoindoline-1,3-Dione: Methods of Using and Compositions Thereof," issued September 23, 2008 (Compl. ¶36).
  • The Invention Explained:
    • Problem Addressed: The patent's background section describes that enhanced or unregulated production of Tumor Necrosis Factor alpha (TNF-α) is implicated in a number of inflammatory, autoimmune, and other diseases (Compl. Ex. B, ’638 Patent, col. 2:21-30). While inhibition of phosphodiesterase type IV (PDE4) can be an effective therapeutic strategy, existing PDE4 inhibitors are described as lacking selective action at acceptable therapeutic doses (’638 Patent, col. 2:64-66).
    • The Patented Solution: The invention is directed to the stereomerically pure (+) enantiomer of a specific chemical compound, apremilast, which is purported to inhibit TNF-α production and PDE4 (’638 Patent, col. 7:20-24, Abstract). The patent asserts that this specific, isolated enantiomer possesses "increased potency and other benefits as compared to its racemate" (a mixture of both enantiomers) (’638 Patent, col. 4:25-29).
    • Technical Importance: The invention provided a specific, purified active pharmaceutical ingredient intended to be a more potent and selective treatment for inflammatory diseases compared to the previously known racemic mixture.
  • Key Claims at a Glance:
    • The complaint broadly alleges infringement of claims reciting the compound or compositions containing it (Compl. ¶51). Independent claim 13 is a representative composition of matter claim.
    • Independent Claim 13 elements:
      • Stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione,
      • substantially free of its (-) isomer,
      • or a pharmaceutically acceptable metabolite, salt, solvate or hydrate, thereof.

U.S. Patent No. 9,872,854

  • Patent Identification: U.S. Patent No. 9,872,854, titled "Methods For the Treatment of Psoriatic Arthritis Using Apremilast," issued January 23, 2018 (Compl. ¶37).
  • The Invention Explained:
    • Problem Addressed: The patent's background identifies a need for safe and effective methods of treating psoriatic arthritis, a chronic inflammatory condition, particularly for patients who are refractory to conventional therapies or in order to reduce side effects associated with such therapies (’854 Patent, col. 2:10-19).
    • The Patented Solution: The patent claims a specific method of treating psoriatic arthritis by orally administering apremilast according to a defined, escalating dosage schedule over an initial six-day period (’854 Patent, col. 5:11-31). This titration schedule is designed to gradually increase the dose to a final maintenance level, a strategy often used to manage potential side effects of a medication (’854 Patent, col. 2:40-51).
    • Technical Importance: The claimed dosing regimen provides a specific therapeutic protocol intended to safely and effectively administer apremilast for psoriatic arthritis while mitigating adverse gastrointestinal symptoms associated with the drug's initial use.
  • Key Claims at a Glance:
    • The complaint alleges infringement of claims reciting methods of administering the compound (Compl. ¶75). Independent claim 1 is the primary method claim.
    • Independent Claim 1 elements:
      • A method of treating psoriatic arthritis,
      • which comprises orally administering escalating doses of stereomerically pure apremilast,
      • wherein the method consists of a specific six-day dosing schedule:
        • Day 1: 10 mg in the morning
        • Day 2: 10 mg in the morning and 10 mg after noon
        • Day 3: 10 mg in the morning and 20 mg after noon
        • Day 4: 20 mg in the morning and 20 mg after noon
        • Day 5: 20 mg in the morning and 30 mg after noon
        • Day 6 and thereafter: 30 mg in the morning and 30 mg after noon

III. The Accused Instrumentality

Product Identification

  • The accused products are Defendants' proposed generic versions of OTEZLA® (apremilast) tablets in 10 mg, 20 mg, and 30 mg dosage strengths, as described in ANDA No. 211681 ("Emcure's Infringing ANDA Products") (Compl. ¶¶1, 39).

Functionality and Market Context

  • The products are oral tablets containing apremilast as the active pharmaceutical ingredient (Compl. ¶39). The complaint alleges that Defendants seek FDA approval to market these generic tablets for the same indications as OTEZLA®, which includes the treatment of active psoriatic arthritis (Compl. ¶¶1, 30). The complaint attaches the prescribing information for OTEZLA® as Exhibit A, which contains a table outlining the specific dosage titration schedule for initiating therapy (Compl. Ex. A, p. 28). This "Dosage Titration Schedule" table specifies the exact escalating daily doses over a six-day period that are recited in claim 1 of the ’854 Patent.

IV. Analysis of Infringement Allegations

’638 Patent Infringement Allegations

Claim Element (from Independent Claim 13) Alleged Infringing Functionality Complaint Citation Patent Citation
Stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, substantially free of its (-) isomer... The complaint alleges, on information and belief, that "Emcure's Infringing ANDA Products contain (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione." ¶52, ¶64 col. 4:48-64
  • Identified Points of Contention:
    • Scope Questions: A central issue may be the construction of "stereomerically pure" and "substantially free of its (-) isomer." The patent provides a definition for "stereomerically pure" as comprising "greater than about 80% by weight of one stereoisomer," with preferred embodiments reaching over 97% (’638 Patent, col. 6:13-32). The dispute may focus on whether the accused generic product's purity meets the construed threshold for infringement.
    • Technical Questions: A key factual question will be the actual chemical composition and enantiomeric purity of the apremilast in Defendants' proposed generic product.

’854 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating psoriatic arthritis, which comprises orally administering... escalating doses... wherein the method consists of the following dosing schedule: [specific 6-day schedule] The complaint alleges that Defendants' proposed product label and insert will include instructions for administration that are "substantially similar" to those for OTEZLA®, and that following these instructions will necessarily result in performance of the claimed method steps. ¶78, ¶89, Ex. A col. 2:40-51
  • Identified Points of Contention:
    • Scope Questions: The use of the transitional phrase "consists of" in claim 1 creates a closed-ended claim, meaning infringement requires performance of the listed steps and no others. The analysis may question whether the instructions on the accused product's label teach any additional or different steps that would take the prescribed method outside the scope of the claim.
    • Technical Questions: An evidentiary question will be whether the final, FDA-approved prescribing information for Defendants' generic product instructs physicians and patients to follow the exact titration schedule claimed in the patent, thereby supporting the allegation of induced infringement.

V. Key Claim Terms for Construction

  • The Term: "stereomerically pure" / "substantially free of its (-) isomer" (from '638 Patent)

  • Context and Importance: The definition of these terms is critical for the composition of matter claims in the ’638 Patent. The infringement analysis will depend on the level of purity required by the claims and whether the defendants' product meets that level. Practitioners may focus on this term because it directly qualifies the claimed chemical entity itself.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides an explicit definition for "stereomerically pure" as a composition that comprises "greater than about 80% by weight of one stereoisomer of the compound and less than about 20% by weight of other stereoisomers" (’638 Patent, col. 6:13-24). A party could argue this express definition should control.
    • Evidence for a Narrower Interpretation: The same section of the specification provides a hierarchy of purity, stating it is "more preferably greater than about 90%," "even more preferably greater than about 95%," and "most preferably greater than about 97%" by weight of one stereoisomer (’638 Patent, col. 6:21-32). A party could argue that these preferred embodiments, combined with the patent's emphasis on the "increased potency" of the pure enantiomer, suggest that one of ordinary skill in the art would understand the invention to require a higher degree of purity than 80%.

  • The Term: "consists of" (from '854 Patent)

  • Context and Importance: This transitional phrase in the preamble of method claim 1 is a term of art that creates a strong presumption that the claim is "closed," meaning it recites only the enumerated steps. This is critical for infringement, as a method that includes additional, unrecited steps would typically not infringe a "consisting of" claim.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: It would be difficult to argue for a broad interpretation. A party might argue that unstated but inherent preliminary steps (e.g., obtaining the medication) or subsequent steps (e.g., monitoring side effects) do not remove the instructed method from the claim's scope, as the core of the method consists of the recited administration steps.
    • Evidence for a Narrower Interpretation: The term "consists of" is a well-established term of art in patent law that signifies a closed scope. The plain language of the claim, which enumerates a precise six-day schedule, provides strong intrinsic evidence that the claim is limited to that exact sequence of steps and no more.

VI. Other Allegations

  • Indirect Infringement: The complaint makes explicit allegations of induced infringement, particularly for the ’854 method patent. It asserts that Defendants will knowingly and intentionally cause infringement by distributing their generic product with a label and insert that instruct physicians and patients to perform the patented dosing method (Compl. ¶¶55, 78).
  • Willful Infringement: The complaint alleges that Defendants had actual and constructive notice of the Patents-in-Suit prior to filing their ANDA and proceeded without adequate justification for their assertions of non-infringement or invalidity (Compl. ¶¶56, 59, 79, 82). This forms the basis for a request for enhanced damages and a finding that the case is "exceptional" under 35 U.S.C. § 285 (Compl. ¶¶59, 82).

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

  • A central issue for the ’638 Patent will be one of chemical purity: does the active pharmaceutical ingredient in Defendants' proposed generic product possess the specific (+) stereochemical configuration at a purity level that falls within the scope of the claim term "stereomerically pure... and substantially free of its (-) isomer," as that term is construed by the court?
  • A core question for the ’854 Patent will be one of induced infringement: will the instructions for use on the final, FDA-approved label of Defendants' generic product direct users to perform the exact, closed-ended, six-day dose-escalation schedule recited in claim 1, thereby establishing the act of infringement and the requisite intent to induce?