DCT

3:23-cv-09763

Alkermes Pharma Ireland Ltd v. Nanjing Delova Biotech Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 3:23-cv-09763, D.N.J., 08/24/2023
  • Venue Allegations: Venue is alleged to be proper on the basis that the Defendant is a foreign corporation headquartered in China and may therefore be sued in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of a New Drug Application (NDA) for a generic version of Plaintiff's ANJESO® product constitutes an act of infringement of four patents related to nanoparticulate meloxicam formulations and methods of use.
  • Technical Context: The technology concerns intravenous formulations of meloxicam, a non-steroidal anti-inflammatory drug (NSAID), developed using nanoparticulate technology to enable rapid onset of action for the management of acute pain.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following Defendant’s submission of an NDA with a Paragraph IV certification for its proposed generic meloxicam injection. Plaintiff received a notice letter from Defendant regarding the NDA filing on or about July 10, 2023. The complaint alleges that Defendant’s initial notice and subsequent disclosures were deficient and delayed.

Case Timeline

Date Event
2009-05-27 ’746 Patent Priority Date
2010-05-26 ’713 Patent Priority Date
2018-03-08 ’663 and ’145 Patents Priority Date
2018-05-22 ’746 Patent Issue Date
2020-02-20 ANJESO® (Reference Drug) NDA Approval Date
2020-07-14 ’713 Patent Issue Date
2021-01-05 ’663 Patent Issue Date
2022-10-04 ’145 Patent Issue Date
2023-07-10 Date of Defendant's Notice Letter to Plaintiff
2023-08-22 Date Defendant provided noninfringement positions to Plaintiff
2023-08-24 Complaint Filing Date

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

U.S. Patent No. 9,974,746 - "Reduction of flake-like aggregation in nanoparticulate active agent compositions"

  • Issued: May 22, 2018

The Invention Explained

  • Problem Addressed: The patent describes a problem specific to nanoparticulate drug formulations intended for injection, wherein "flake-like" aggregates can form at the air-liquid interface (Compl. Ex. A, ’746 Patent, col. 1:49-55). These aggregates, while not always detectable by standard light-scattering particle sizers, can cause the formulation to fail the microscopic particulate matter standards required by the United States Pharmacopeia (USP <788>), rendering it unsuitable for injection (Compl. Ex. A, ’746 Patent, col. 2:1-8).
  • The Patented Solution: The invention is a composition and method that reduces this flake-like aggregation by incorporating a "flake-like aggregation reducing agent" into the nanoparticulate dispersion (Compl. Ex. A, ’746 Patent, Abstract). This agent can be a specific sugar (such as sucrose or mannitol) or a pH buffer that maintains the formulation at a pH above 7.0, both of which are shown to prevent the formation of these large, two-dimensional aggregates and improve the stability and safety of the injectable product (Compl. Ex. A, ’746 Patent, col. 7:35-43).
  • Technical Importance: This solution enables the development of stable, "ready-for-use" injectable nanoparticulate formulations of poorly soluble drugs that can meet stringent regulatory standards for particulate matter (Compl. Ex. A, ’746 Patent, col. 2:9-18).

Key Claims at a Glance

The complaint does not identify specific asserted claims, alleging infringement of "one or more claims" (Compl. ¶46). Independent claim 1 is representative and includes the following essential elements:

  • An injectable nanoparticulate active agent composition produced by a method for reducing flake-like aggregates.
  • The method comprises preparing a dispersion of a nanoparticulate active agent and at least one surface stabilizer.
  • The method further comprises adding a flake-like aggregation reducing agent to the dispersion.
  • The reducing agent is selected from a specified group of buffers or a specified group of sugars (sucrose, mannitol, or dextrose).
  • The final composition meets USP particulate matter limits (no more than 6,000 particles >10 µm and no more than 600 particles >25 µm).

U.S. Patent No. 10,709,713 - "Nanoparticulate meloxicam formulations"

  • Issued: July 14, 2020

The Invention Explained

  • Problem Addressed: Meloxicam, an effective NSAID, is poorly soluble in water, which results in a slow onset of action when administered orally (Tmax of 4-6 hours) (Compl. Ex. B, ’713 Patent, col. 7:40-45). This delayed action makes conventional oral meloxicam inappropriate for managing acute pain where rapid relief is required (Compl. Ex. B, ’713 Patent, col. 5:47-51).
  • The Patented Solution: The patent discloses a formulation of meloxicam as nanoparticles (particles with an average size of less than 2000 nm) combined with a surface stabilizer (Compl. Ex. B, ’713 Patent, Abstract). Reducing the particle size to the nanometer scale dramatically increases the surface area, which in turn increases the rate of dissolution. This enhanced dissolution rate allows for an injectable formulation that can be administered intravenously for a rapid onset of pain relief (Compl. Ex. B, ’713 Patent, col. 7:26-34).
  • Technical Importance: The invention provides a way to transform a slow-acting oral NSAID into a fast-acting, non-opioid injectable analgesic for treating moderate to moderately severe acute pain (Compl. Ex. B, ’713 Patent, col. 6:10-15).

Key Claims at a Glance

The complaint does not identify specific asserted claims, alleging infringement of "one or more claims" (Compl. ¶60). Independent claim 1 is representative and includes the following essential elements:

  • A method for treating moderate to severe pain in an adult human.
  • The method comprises administering a once-daily intravenous bolus injection of a specific meloxicam formulation.
  • The administration achieves a specific mean pharmacokinetic profile (AUCinf of 107508.7 ± 34443.0 ng*hr/ml).
  • The formulation "consists of" 30 mg of nanoparticulate meloxicam, water, a surface stabilizer, and a pharmaceutically acceptable excipient.
  • The nanoparticulate meloxicam has an effective average particle size of less than about 150 nm.
  • The formulation meets USP particulate matter limits.
  • The surface stabilizer is adsorbed on the particle surface and is "essentially free of intermolecular cross-linkages."

U.S. Patent No. 10,881,663 - "Method of treating pain in elderly patients with mild renal impairment"

  • Patent Identification: 10,881,663, issued January 5, 2021 (Compl. ¶21).
  • Technology Synopsis: This patent addresses the specific clinical challenge of treating pain in elderly patients (at least 65 years old) who also have mild renal impairment, a patient population particularly vulnerable to NSAID-related side effects (Compl. Ex. C, ’663 Patent, col. 2:1-9). The invention is a method of treatment claiming that a 30 mg intravenous dose of meloxicam is safe and effective in this subpopulation without the dose adjustments typically required for NSAIDs, a finding described as surprising (Compl. Ex. C, ’663 Patent, col. 5:5-24).
  • Asserted Claims: The complaint does not specify claims; independent claims 1 and 15 are asserted in related litigation and are representative.
  • Accused Features: Defendant's proposed generic meloxicam injection, by seeking approval for the same indications as ANJESO®, is alleged to be intended for use in the claimed patient population, thereby infringing the patented method (Compl. ¶74).

U.S. Patent No. 11,458,145 - "Methods of administering intravenous meloxicam in a bolus dose"

  • Patent Identification: 11,458,145, issued October 4, 2022 (Compl. ¶22).
  • Technology Synopsis: This patent focuses on the method of administering the intravenous meloxicam formulation. The invention recognizes that rapid injection of other IV NSAIDs can cause significant injection site pain (Compl. Ex. D, ’145 Patent, col. 1:46-53). The claimed method involves administering the nanoparticulate meloxicam as a rapid bolus dose (e.g., over 15 to 30 seconds), which provides a fast onset of pain relief without this adverse effect (Compl. Ex. D, ’145 Patent, col. 2:7-11).
  • Asserted Claims: The complaint does not specify claims; independent claims 1 and 6 are representative.
  • Accused Features: Defendant's product is a "meloxicam injection" intended to be administered in the same manner as ANJESO®, which is given as a bolus dose. The filing of the NDA is alleged to be an act of infringement of this patented method (Compl. ¶88).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendant's "Proposed Drug Product," identified as a "meloxicam injection" at a concentration of 30 mg/mL, intended to be administered as a 30 mg dose (Compl. ¶1, 27).
  • Functionality and Market Context: The Proposed Drug Product is a generic version of Plaintiff's ANJESO®, which is an intravenous NSAID indicated for the management of moderate-to-severe pain (Compl. ¶1, 15, 18). The legal basis for the suit is Defendant's filing of an NDA with the FDA under the Hatch-Waxman Act, seeking approval to commercially manufacture and sell this generic version in the United States prior to the expiration of the patents-in-suit (Compl. ¶1, 23). The act of filing the NDA with a Paragraph IV certification constitutes a statutory act of infringement (Compl. ¶26).
  • Visual Evidence: No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint makes general allegations that the Proposed Drug Product will infringe one or more claims of each patent-in-suit but does not provide a claim chart or specific details of its infringement theory (Compl. ¶¶46, 60, 74, 88). In a Hatch-Waxman case, the infringement allegation is predicated on the requirement that a generic product must have the same active ingredient, dosage form, strength, and conditions of use as the reference listed drug. The following summary is based on this predicate.

’746 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
An injectable nanoparticulate active agent composition... Defendant's product is an injectable meloxicam formulation alleged to be a generic version of ANJESO®, which is based on nanoparticulate technology. ¶¶1, 27, 46 col. 7:20-22
...adding a flake-like aggregation reducing agent to the... dispersion, wherein the flake-like aggregation reducing agent is selected from... a sugar selected from the group consisting of sucrose mannitol and dextrose... The ANJESO® formulation, which the Proposed Drug Product is alleged to copy, contains sucrose, which functions as the claimed reducing agent. ¶¶1, 46 col. 8:35-43
...wherein the composition comprises no more than 6,000 active agent particles that are greater than 10 µm in size and no more than 600 active agent particles that are greater than 25 µm in size. To gain FDA approval, Defendant’s injectable product must meet the particulate matter standards of USP <788>, which correspond to the limits recited in the claim. ¶¶23, 26, 46 col. 8:54-59

’713 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating moderate to severe pain in an adult human in need thereof comprising: administering once a day to the adult human an intravenous bolus injection of a meloxicam formulation... The proposed label for Defendant’s product is alleged to instruct for the same method of use as ANJESO®: once-daily IV bolus injection for moderate to severe pain. ¶¶1, 18, 60 col. 29:5-8
...wherein the meloxicam formulation consists of 30 milligrams of nanoparticulate meloxicam, water, a surface stabilizer and a pharmaceutically acceptable excipient... Defendant’s product is a 30 mg injection alleged to have the same formulation as ANJESO®, which contains these components. ¶¶1, 27, 60 col. 29:11-15
...wherein the nanoparticulate meloxicam has an effective average particle size of less than about 150 nm... As a generic equivalent, the Proposed Drug Product is alleged to utilize meloxicam with the same nanoparticulate size characteristics as that used in ANJESO®. ¶¶1, 60 col. 29:15-17
...to achieve a mean AUCinf of 107508.7±34443.0 ng*hr/ml in the adult human... To be approved as a generic, Defendant must demonstrate that its product is bioequivalent to ANJESO®, which would require it to achieve a comparable pharmacokinetic profile, including the claimed AUCinf. ¶¶1, 15, 60 col. 29:9-11
  • Identified Points of Contention:
    • Evidentiary Questions: The complaint lacks specific factual allegations linking the Proposed Drug Product to the claim limitations. A central issue will be what the evidence contained within Defendant’s confidential NDA submission reveals about its specific formulation, particle size distribution, manufacturing process, and bioequivalence data.
    • Scope Questions: For the ’746 patent, which includes product-by-process claims, a potential dispute is whether Defendant’s manufacturing method is the same as the claimed method. For the ’713 patent, the use of the restrictive term "consists of" raises the question of whether Defendant’s formulation contains any additional, unrecited components that might place it outside the literal scope of the claim.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail for analysis of potential claim construction disputes. However, based on the patent language, certain terms may become central to the case.

  • The Term: "flake-like aggregation reducing agent" (’746 Patent)

  • Context and Importance: This term is central to the novelty of the ’746 patent. Its construction will determine whether common pharmaceutical excipients, such as the sucrose allegedly used in the accused product, fall within the claim scope when used in a nanoparticulate formulation for the claimed purpose.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification provides a functional definition, describing the agent as one that is "capable of reducing the flake-like aggregation" (Compl. Ex. A, ’746 Patent, col. 17:5-8). This could support an argument that the term should be defined by its function.
    • Evidence for a Narrower Interpretation: Claim 1 states the agent "is selected from the group consisting of" specific buffers and sugars (Compl. Ex. A, ’746 Patent, col. 37:44-50). The phrase "consisting of" is strongly limiting in patent law, suggesting the claim is closed to any agents not explicitly listed.

  • The Term: "consists of" (’713 Patent)

  • Context and Importance: This term defines the claimed formulation in claim 1 of the ’713 patent. Because "consists of" is a term of art that excludes any elements not specified, its interpretation is critical. If Defendant’s formulation includes any additional active or inactive ingredients not encompassed by "meloxicam, water, a surface stabilizer and a pharmaceutically acceptable excipient," it may not literally infringe.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The term "pharmaceutically acceptable excipient" is itself broad and could be argued to encompass a range of other necessary formulation components beyond the stabilizer and water (Compl. Ex. B, ’713 Patent, col. 29:14-15).
    • Evidence for a Narrower Interpretation: The plain meaning of "consists of" creates a strong presumption that the list of ingredients is exhaustive. The patent does not appear to contain language redefining this standard interpretation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will induce and contribute to infringement of all four patents (e.g., Compl. ¶¶50-51, 64-65). The basis for inducement is the allegation that Defendant will intentionally encourage infringement through the sale and marketing of its product with knowledge of the patents. The basis for contributory infringement is the allegation that the product is especially adapted for an infringing use and has no substantial non-infringing use (e.g., Compl. ¶51).
  • Willful Infringement: The complaint does not use the term "willful," but it alleges that Defendant has knowledge of the patents-in-suit (Compl. ¶50) and asserts that the case is "exceptional," seeking an award of attorneys' fees under 35 U.S.C. § 285 (Compl. ¶56). These allegations form the basis for a potential future claim of willfulness based on pre-suit knowledge stemming from the Paragraph IV notice letter.

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

  • A central issue will be one of factual proof: As is common in initial Hatch-Waxman complaints, the infringement allegations are conclusory. The case will turn on evidence from Defendant's confidential NDA, which will reveal whether its proposed generic product's formulation, particle size, pharmacokinetic profile, and intended use actually fall within the scope of the asserted patent claims.
  • A key legal question will be one of claim scope and infringement: The litigation may focus on whether restrictive claim language, such as "consists of" in the ’713 patent, can be overcome, and whether infringement of method-of-treatment claims (’663 and ’145 patents) can be established based on the proposed product label and intended market.
  • A procedural question relates to pre-suit conduct: The complaint alleges deficiencies in Defendant's Paragraph IV notice letter and subsequent disclosures (Compl. ¶¶31-35). While not determinative of infringement, disputes over the adequacy of these statutory disclosures could influence early case management and discovery.