DCT

1:18-cv-00599

iCeutica Pty Ltd v. Novitium Pharma LLC

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: iCeutica Pty Ltd v. Novitium Pharma LLC, 1:18-cv-00599, D. Del., 04/20/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because the defendant, Novitium Pharma LLC, is incorporated in Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic meloxicam capsules constitutes an act of infringement of three patents covering low-dose, nanoparticle formulations of the drug.
  • Technical Context: The technology involves creating formulations of the non-steroidal anti-inflammatory drug (NSAID) meloxicam with reduced particle sizes to improve dissolution and achieve specific pharmacokinetic profiles, enabling effective pain management for conditions like osteoarthritis at lower systemic exposures.
  • Key Procedural History: This is a Hatch-Waxman action triggered by Defendant's ANDA filing with a Paragraph IV certification. Plaintiffs' VIVLODEX® (meloxicam) is the reference listed drug, and the patents-in-suit are listed in the FDA's Orange Book as covering the product. The complaint notes that Defendant’s Paragraph IV letter asserts non-infringement and/or invalidity of the patents. The complaint also states that prior to filing suit, the parties were unable to agree on terms for Plaintiffs to access the ANDA file.

Case Timeline

Date Event
2014-06-09 Priority Date for ’734, ’318, and ’468 Patents
2016-12-27 U.S. Patent No. 9,526,734 Issues
2017-05-16 U.S. Patent No. 9,649,318 Issues
2017-11-07 U.S. Patent No. 9,808,468 Issues
2018-03-09 Date of Defendant's Paragraph IV Letter
2018-03-12 Plaintiffs Receive Defendant's Paragraph IV Letter
2018-04-20 Complaint Filing Date

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

U.S. Patent No. 9,526,734 - “Formulation of Meloxicam”

  • Patent Identification: U.S. Patent No. 9,526,734, entitled “Formulation of Meloxicam,” issued on December 27, 2016 (’734 Patent).

The Invention Explained

  • Problem Addressed: The patent’s background section highlights the serious, dose-related side effects associated with NSAIDs like meloxicam, including gastrointestinal and cardiovascular events. This led the FDA to recommend using the lowest effective dose for the shortest duration possible. The patent also notes that meloxicam's poor water solubility presents a challenge for oral absorption. (’734 Patent, col. 1:25-52).
  • The Patented Solution: The invention is a low-dose (e.g., 5 mg) formulation of meloxicam composed of nanoparticles. By reducing the particle size of the drug, the formulation aims to increase the dissolution rate and improve absorption, thereby achieving therapeutic effectiveness at a lower systemic exposure (AUC) compared to conventional, higher-dose products like Mobic®. The patent claims specific particle size distributions and resulting pharmacokinetic (PK) profiles. (’734 Patent, Abstract; col. 2:6-15).
  • Technical Importance: This approach seeks to provide a safer NSAID therapy option by enabling a lower dose of meloxicam to be effective for pain relief. (’734 Patent, col. 1:41-48).

Key Claims at a Glance

The complaint asserts infringement of one or more unspecified claims (Compl. ¶33). Independent claim 1 is representative of the patented composition:

  • A capsule form of a pharmaceutical composition comprising 5 mg of meloxicam.
  • The meloxicam has a median particle size on a volume basis between 100 nm and 500 nm.
  • The meloxicam has a D(0.9) particle size distribution between 1200 nm and 3000 nm.
  • A single capsule, administered to a population of healthy adults in a fasted state, provides a mean plasma AUC (0-∞) of 7500-20000 h*ng/ml and a mean plasma Cmax of 350-950 ng/ml.
  • The capsule has a dissolution rate where at least 80% of the meloxicam dissolves in 10 minutes or less under specified test conditions.

U.S. Patent No. 9,649,318 - “Formulation of Meloxicam”

  • Patent Identification: U.S. Patent No. 9,649,318, entitled “Formulation of Meloxicam,” issued on May 16, 2017 (’318 Patent).

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’734 Patent, the ’318 Patent addresses the same technical problem: the need for a lower-dose, effective meloxicam formulation to mitigate the risk of dose-related NSAID side effects, while overcoming the drug's poor solubility. (’318 Patent, col. 1:25-52).
  • The Patented Solution: The patented solution is again a low-dose meloxicam composition with specific nanoparticle and pharmacokinetic characteristics designed to provide effective pain relief with reduced systemic exposure. The detailed description largely mirrors that of the ’734 Patent. (’318 Patent, Abstract; col. 2:6-15).
  • Technical Importance: The invention provides an alternative formulation pathway to achieve the clinical goal of a lower-dose, effective NSAID. (’318 Patent, col. 1:41-48).

Key Claims at a Glance

The complaint asserts infringement of one or more unspecified claims (Compl. ¶65). Independent claim 1 is representative:

  • A capsule form of a pharmaceutical composition comprising 5 mg of meloxicam.
  • The meloxicam has a median particle size on a volume basis between 100 nm and 1000 nm.
  • The meloxicam has a D(0.9) particle size distribution of less than 4000 nm and greater than 1200 nm.
  • A single capsule, administered to a population of healthy adults in a fasted state, provides a mean plasma AUC (0-∞) of 7500-20000 h*ng/ml and a mean plasma Cmax of 350-950 ng/ml.
  • The capsule has a dissolution rate where at least 80% of the meloxicam dissolves in 10 minutes or less under specified test conditions.

U.S. Patent No. 9,808,468 - “Formulation of Meloxicam”

  • Patent Identification: U.S. Patent No. 9,808,468, entitled “Formulation of Meloxicam,” issued on November 7, 2017 (’468 Patent).
  • Technology Synopsis: This patent is part of the same family and is directed to methods of treating osteoarthritis. The technical basis is the same as the ’734 and ’318 patents: the administration of a low-dose, nanoparticle meloxicam formulation that provides a specific dissolution and pharmacokinetic profile to effectively manage pain. (’468 Patent, Abstract; col. 1:25-52).
  • Asserted Claims: The complaint alleges infringement of one or more of the method claims (Compl. ¶93). Independent claim 1 is a representative method claim for treating osteoarthritis by administering a 5 mg capsule with specified particle size and dissolution properties.
  • Accused Features: The complaint alleges that the product label and instructions for use for Defendant's proposed generic product will instruct physicians and patients to perform the patented methods of treatment, thereby inducing infringement. (Compl. ¶¶93-94, 98-101).

III. The Accused Instrumentality

Product Identification

  • Defendant’s proposed generic Meloxicam capsules, in 5 mg and 10 mg dosages, which are the subject of ANDA No. 211398 (Compl. ¶25).

Functionality and Market Context

  • The complaint alleges the accused product is a "generic version of the VIVLODEX® product" (Compl. ¶25). As such, its intended function is to provide pain relief for conditions like osteoarthritis and to be therapeutically equivalent to the branded drug. The complaint alleges that to achieve this, the accused product will necessarily embody the patented technology, including the specific nanoparticle formulations and resulting pharmacokinetic profiles (Compl. ¶¶22, 33). The product is intended to compete directly with VIVLODEX® upon receiving FDA approval (Compl. ¶29).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

The complaint does not contain a claim chart or detailed element-by-element infringement allegations, as Plaintiffs have not yet obtained the Defendant's ANDA (Compl. ¶¶32-33). The infringement theory is based on the allegation that the accused ANDA product is a generic version of VIVLODEX® and is therefore covered by the patents-in-suit (Compl. ¶¶22, 25).

U.S. 9,526,734 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A capsule form of a pharmaceutical composition comprising 5 mg of meloxicam The complaint alleges Defendant seeks approval for 5 mg and 10 mg generic meloxicam capsules via its ANDA. ¶25 col. 25:35-37
having a median particle size, on a volume basis, between 100 nm and 500 nm and a D(0.9) that is between 1200 nm and 3000 nm The complaint alleges on information and belief that the proposed generic product falls within the scope of the claims, which require this particle size distribution. ¶33 col. 25:38-41
wherein a single capsule, upon oral administration ... provides a mean plasma AUC (0-∞) of 7500-20000 h*ng/ml and a mean plasma Cmax of 350-950 ng/ml The complaint alleges the ANDA product is a generic version of VIVLODEX® and will thus exhibit the pharmacokinetic profile covered by the claims. ¶¶22, 25, 33 col. 25:41-47
wherein the dissolution rate is such that ... at least 80% of the meloxicam dissolves in 10 minutes or less The complaint alleges the proposed generic product will have the dissolution properties of the claimed invention to be therapeutically equivalent to VIVLODEX®. ¶¶22, 25, 33 col. 25:47-52

U.S. 9,649,318 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A capsule form of a pharmaceutical composition comprising 5 mg of meloxicam Defendant's ANDA is for 5 mg and 10 mg generic meloxicam capsules. ¶25 col. 25:35-37
having a median particle size, on a volume basis, between 100 nm and 1000 nm, wherein the D(0.9) ... is less than 4000 nm and greater than 1200 nm On information and belief, the complaint alleges the proposed generic product will have the particle size characteristics recited in the claims. ¶¶33, 65 col. 25:38-44
wherein a single dose, upon oral administration... provides a mean plasma AUC (0-∞) that is 80% to 125% of 13610 ng-h/ml As a proposed generic equivalent to VIVLODEX®, the ANDA product is alleged to meet the bioequivalence and PK parameters recited in the claims. ¶¶22, 25, 65 col. 26:9-12
wherein the dissolution rate is such that ... at least 80% of the meloxicam dissolves in 10 minutes or less As a proposed generic, the ANDA product is alleged to have the dissolution properties required by the claims to be equivalent to VIVLODEX®. ¶¶22, 25, 65 col. 25:47-50

Identified Points of Contention

  • Technical Questions: The central dispute will be factual and technical: does the formulation described in Defendant's confidential ANDA actually meet the specific numerical limitations for particle size, dissolution rate, and pharmacokinetic parameters recited in the asserted claims? The complaint's allegations are made on "information and belief" pending discovery of the ANDA.
  • Scope Questions: A potential point of contention may be whether the test methods used by the Defendant to characterize its product (e.g., for particle size or dissolution) are the same as those contemplated by the patent. The interpretation of how to measure and define these parameters could be critical to the infringement analysis.

V. Key Claim Terms for Construction

  • The Term: "median particle size, on a volume average basis"

  • Context and Importance: The invention is defined by specific, narrow ranges of nanoparticle sizes. The precise methodology for measuring this property is critical to determining whether a product falls within the claim scope. Practitioners may focus on this term because different measurement instruments or settings can produce different results, potentially moving an accused product inside or outside the claimed range.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification states that a "wide range of techniques can be utilized to characterize the particle size of a material" and mentions laser diffraction as one such method, which may support the view that any scientifically valid, standard technique is acceptable ('734 Patent, col. 13:1-8).
    • Evidence for a Narrower Interpretation: Example 1 of the patent discloses using a specific instrument (Malvern Mastersizer 2000) with highly specific pump and measurement settings to determine particle size. A party could argue that the claims should be interpreted in light of this specific disclosure. ('734 Patent, col. 19:46-64).

  • The Term: "a population of healthy adults"

  • Context and Importance: The pharmacokinetic parameters (AUC and Cmax) central to the claims are defined by administration to this group. The definition of this population (e.g., number of subjects, demographic criteria) is essential for comparing the results of different clinical studies.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The term itself is general and could be argued to encompass any group of subjects that would be considered "healthy adults" under standard FDA guidelines for bioequivalence studies.
    • Evidence for a Narrower Interpretation: The patent includes a clinical trial summary in Example 3 and Table 3. A party might argue that "a population of healthy adults" should be construed as a population with characteristics comparable to the one used in the patent's own supporting clinical trial. ('734 Patent, col. 20:64-col. 22:27).

VI. Other Allegations

Indirect Infringement

  • The complaint alleges active inducement of the method claims of the ’468 patent, stating that Defendant’s product labeling and instructions will direct medical professionals and patients to use the generic capsules in a manner that performs the claimed method of treating osteoarthritis (Compl. ¶¶93-94, 98). The complaint also alleges contributory infringement, asserting the proposed product is a material part of the invention and has no substantial non-infringing uses (Compl. ¶¶95-96).

Willful Infringement

  • The complaint alleges willfulness based on pre-suit knowledge. It states that Defendant became aware of the patents-in-suit "no later than when each patent was issued by the Patent Office and/or listed in the Orange Book" (Compl. ¶¶57, 85, 97). The complaint further alleges that Defendant's filing of a Paragraph IV certification demonstrates actual knowledge and that it proceeded to infringe (or was willfully blind to infringement) despite this knowledge (Compl. ¶¶58, 86, 98).

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

  • A central issue will be one of technical fact-finding: Once the ANDA is produced in discovery, does the Defendant's proposed generic meloxicam formulation fall within the specific, quantitative boundaries for particle size, dissolution, and pharmacokinetic parameters recited in the asserted claims? The outcome will depend entirely on a comparison of the ANDA data against the claim language.
  • A key antecedent question will be one of claim construction: How will the court define the methodologies for measuring the claimed properties? The construction of terms like "median particle size" and the protocol for determining pharmacokinetic values in "a population of healthy adults" will establish the framework for the technical infringement analysis.
  • Finally, the case will present a fundamental question of validity versus infringement: While the complaint alleges infringement, Defendant's Paragraph IV certification puts the validity of the patents directly at issue. The core of the case will therefore be a two-part inquiry: assuming the claims are valid, does the accused ANDA product infringe; and are the claims, which are directed to specific formulations of a known drug, in fact valid over the prior art?