DCT

1:20-cv-01094

Azurity Pharma Inc v. Alkem Laboratories Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-01094, D. Del., 09/30/2020
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because it is a likely destination for the accused product and because Defendant Alkem regularly transacts business and has engaged in prior patent litigation in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of Plaintiff's FIRVANQ® product constitutes an act of infringement of two patents related to stable oral liquid formulations of vancomycin hydrochloride.
  • Technical Context: The patents concern formulations of vancomycin, an antibiotic used to treat serious intestinal infections like Clostridium difficile-associated diarrhea, into a stable and palatable oral liquid suitable for patients who cannot take solid capsules.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of notice letters from Defendant. In these letters, Defendant stated it had filed an ANDA with a Paragraph IV Certification, asserting that Plaintiff's patents are invalid, unenforceable, or will not be infringed by Defendant's proposed generic product.

Case Timeline

Date Event
2014-03-14 Earliest Priority Date for ’028 and ’046 Patents
2019-12-03 U.S. Patent No. 10,493,028 Issued
2020-06-23 U.S. Patent No. 10,688,046 Issued
2020-07-07 Defendant Notified Plaintiff of ANDA Filing (’028 Patent Notice)
2020-07-24 Defendant Notified Plaintiff of ANDA Filing (’046 Patent Notice)
2020-09-30 Complaint Filed

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

U.S. Patent No. 10,493,028 - Composition and Method for Vancomycin Oral Liquid

The Invention Explained

  • Problem Addressed: The patent’s background section describes challenges in administering vancomycin orally, particularly to pediatric and geriatric patients who have difficulty swallowing capsules. (’028 Patent, col. 5:1-7). Compounding liquid versions from powder intended for injection is described as cumbersome for pharmacists, potentially unpalatable for patients, and posing a risk of contamination due to the lack of preservatives. (’028 Patent, col. 5:25-50).
  • The Patented Solution: The invention provides a stable, non-sterile liquid formulation of vancomycin hydrochloride, or a kit for preparing it, that is homogenous and stable for at least 30 days at both ambient and refrigerated temperatures. (’028 Patent, col. 2:23-31). The formulation includes specific excipients such as a buffering agent, sweetener, flavoring agent, and a preservative to improve stability and palatability. (’028 Patent, col. 2:51-57). The invention is illustrated in Figure 1 as a kit containing a powder and a liquid solution for combination. (’028 Patent, col. 4:40-42).
  • Technical Importance: The technology aimed to provide a standardized, stable, and easy-to-use oral liquid vancomycin product, thereby improving patient compliance, ensuring consistent dosing, and reducing the risks associated with ad-hoc pharmacy compounding. (’028 Patent, col. 5:50-65).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’028 patent (Compl. ¶38). Independent claim 1 is representative:
    • A non-sterile stable liquid formulation for oral administration, consisting of:
    • (a) 0.1-0.4% w/v anhydrous citric acid,
    • (b) water,
    • (c) 0.1-0.3% w/v sucralose,
    • (d) 0.01-0.1% w/v of a flavoring agent,
    • (e) 0.08-0.2% w/v sodium benzoate,
    • (f) 0.0001-0.0003% w/v of a dye, and
    • (g) vancomycin hydrochloride,
    • wherein the formulation is homogenous and stable for at least 30 days at ambient and refrigerated temperatures, has a pH of 2.5-4.5, and a vancomycin concentration of 25-50 mg/ml.
  • The complaint does not explicitly reserve the right to assert dependent claims.

U.S. Patent No. 10,688,046 - Composition and Method for Vancomycin Oral Liquid

The Invention Explained

  • Problem Addressed: As a continuation of the application leading to the ’028 patent, the ’046 Patent addresses the same technical problems: the difficulty of administering solid oral vancomycin to certain patient populations and the cumbersomeness, instability, and contamination risks of compounding liquid versions from sterile powders. (’046 Patent, col. 5:1-50).
  • The Patented Solution: The ’046 Patent similarly discloses a kit and resulting non-sterile liquid formulation of vancomycin hydrochloride designed to be stable and palatable. The solution comprises specific types and concentrations of buffering agents, sweeteners, preservatives, and flavorings to overcome the deficiencies of prior methods. (’046 Patent, col. 2:25-31, 2:55-3:5).
  • Technical Importance: This technology provides an FDA-approved, standardized alternative to pharmacy-compounded oral vancomycin, intended to enhance safety, dosing accuracy, and patient adherence. (’046 Patent, col. 5:50-65).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’046 patent (Compl. ¶47). Independent claim 8 is a representative method claim:
    • A method of treating Clostridium difficile pseudomembranous colitis or Staphylococcal enterocolitis in a subject comprising administering a vancomycin oral liquid composition, wherein the composition consists of:
    • (a) 0.1-0.4% w/v citric acid,
    • (b) water,
    • (c) a sweetener that is sucralose,
    • (d) 0.02-0.08% w/v sodium benzoate,
    • (e) 20-60 mg/ml vancomycin hydrochloride, and
    • (f) a flavoring agent,
    • wherein the composition is homogenous and stable for at least 2 weeks at ambient and refrigerated temperature and has a pH of 2.5-4.5.
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • Defendant Alkem's proposed generic version of Plaintiff's FIRVANQ® product, identified as the subject of ANDA No. 214913 (the "Alkem ANDA Product"). (Compl. ¶1, ¶25).

Functionality and Market Context

  • The complaint alleges that Alkem's ANDA Product is a "kit for oral solution" intended for the same therapeutic uses as FIRVANQ®, namely the treatment of Clostridium difficile-associated diarrhea and staphylococcal enterocolitis. (Compl. ¶12, ¶26, ¶29).
  • By filing an ANDA, Alkem has represented to the FDA that its product has the same active ingredient, route of administration, dosage form, and strength as FIRVANQ® and is bioequivalent to it. (Compl. ¶32). The complaint alleges that the proposed label for the Alkem ANDA Product is "substantially similar, if not identical," to the FIRVANQ® label, which instructs a healthcare provider to reconstitute a powder to produce the final oral solution. (Compl. ¶33, ¶34).

IV. Analysis of Infringement Allegations

The complaint does not contain a claim chart. The following tables summarize the infringement theory as inferred from the complaint's allegations that the Alkem ANDA Product is a bioequivalent generic version of Plaintiff's FIRVANQ® product.

No probative visual evidence provided in complaint.

’028 Patent Infringement Allegations (based on Claim 1)

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A non-sterile stable liquid formulation for oral administration... Alkem's ANDA Product is an oral solution that has the same route of administration, dosage form, and is bioequivalent to Plaintiff's FIRVANQ® product. ¶32 col. 28:32-34
consisting of: ... (g) vancomycin hydrochloride... The Alkem ANDA Product has the same active ingredients as Plaintiff's FIRVANQ® product. ¶32 col. 28:44-45
(a) 0.1-0.4% w/v anhydrous citric acid, (b) water, (c) 0.1-0.3% w/v sucralose, (d) 0.01-0.1% w/v of a flavoring agent, (e) 0.08-0.2% w/v sodium benzoate, (f) 0.0001-0.0003% w/v of a dye... The complaint alleges Alkem's ANDA Product is bioequivalent and has the same dosage form as FIRVANQ®, suggesting the presence of necessary excipients to create the claimed formulation. ¶32 col. 28:35-43
wherein the formulation is homogenous and stable for at least 30 days... and has a pH of 2.5-4.5... The complaint's allegation of bioequivalence suggests Alkem's ANDA Product will possess physical and chemical properties, such as stability and pH, that fall within the claimed ranges. ¶32 col. 28:46-50
and wherein the concentration of vancomycin in the solution is 25-50 mg/ml. The Alkem ANDA Product has the same strength as Plaintiff's FIRVANQ® product. ¶32 col. 28:50-52

’046 Patent Infringement Allegations (based on Claim 8)

Claim Element (from Independent Claim 8) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating Clostridium difficile pseudomembranous colitis or Staphylococcal enterocolitis... Alkem's ANDA Product is indicated for the same treatments as Plaintiff's FIRVANQ® product. ¶12, ¶32 col. 29:7-9
...in a subject comprising administering a vancomycin oral liquid composition... The proposed label for the Alkem ANDA Product is alleged to be substantially similar to the label for FIRVANQ®, which instructs oral administration. ¶34 col. 29:9-11
...wherein the composition consists of: (a) ...citric acid... (c) ...sucralose... (d) ...sodium benzoate... (e) ...vancomycin hydrochloride, and (f) flavoring agent... The Alkem ANDA Product is alleged to be a bioequivalent generic with the same active ingredient and dosage form, suggesting it contains the claimed components. ¶32 col. 29:12-20
...wherein the composition is homogenous and stable for at least 2 weeks...and has a pH of 2.5-4.5. The allegation of bioequivalence suggests the reconstituted Alkem ANDA Product will exhibit the claimed physical and chemical properties. ¶32 col. 29:21-24
  • Identified Points of Contention:
    • Factual Questions: The central dispute will be factual: does the specific formulation disclosed in Alkem's confidential ANDA contain each of the chemical components within the specific concentration ranges required by the asserted claims? The complaint, lacking this information, relies on the legal representation of bioequivalence to infer infringement.
    • Scope Questions: A potential issue may arise concerning the scope of functional limitations, such as "stable for at least 30 days." The question for the court could be whether Alkem's ANDA Product, based on its own stability data, meets this requirement as it would be construed by one of ordinary skill in the art.

V. Key Claim Terms for Construction

  • The Term: "stable for at least 30 days" (’028 Patent, Claim 1); "stable for at least 2 weeks" (’046 Patent, Claim 8).

  • Context and Importance: This term is a functional limitation that defines a key performance characteristic of the invention. The dispute may center on the precise technical criteria (e.g., percentage of degradation, microbial growth) required to meet this "stable" limitation and whether Alkem's product satisfies those criteria.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification describes stability in general terms, such as being "homogenous and stable for at least 30 days at ambient and refrigerated temperature conditions." (’028 Patent, col. 2:27-30). This could support a construction based on general therapeutic suitability over the time period.
    • Evidence for a Narrower Interpretation: The patent provides specific stability data in its examples, showing vancomycin assay results remaining above 100% and pH values within a narrow range over 30 days. (’028 Patent, col. 18, Tables). A party could argue these examples define the scope of "stable" more narrowly.

  • The Term: "homogenous" (’028 Patent, Claim 1; ’046 Patent, Claim 8).

  • Context and Importance: This term is critical for ensuring consistent and accurate dosing. Practitioners may focus on whether this requires a true solution (fully dissolved) or can also read on a uniform suspension where particles are evenly dispersed after shaking, as this could impact whether Alkem's formulation infringes.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification notes that upon shaking, "the vancomycin hydrochloride powder particles are dispersed throughout the liquid form to provide a homogenous solution." (’028 Patent, col. 10:25-28). The use of "dispersed" might suggest that a uniform suspension could be considered "homogenous."
    • Evidence for a Narrower Interpretation: The patent distinguishes between solutions and suspensions, noting that suspensions can cause settling and inaccurate dosing. (’028 Patent, col. 10:30-38). This could support an argument that "homogenous" requires a true solution, free from settling particles.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement. The theory is that Alkem, through its proposed product labeling, will actively encourage and instruct pharmacists and other healthcare providers to reconstitute the Alkem ANDA Product, an act that allegedly results in a directly infringing final formulation. (Compl. ¶40, ¶42, ¶49, ¶51).
  • Willful Infringement: The complaint alleges that Alkem had "actual and constructive knowledge" of the patents prior to or at the time of its ANDA filing and its Paragraph IV certification. (Compl. ¶41, ¶50). This alleged pre-suit knowledge is the basis for the willfulness claim.

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

  • A core issue will be one of evidentiary proof: As this is an ANDA case, the initial complaint is based on public information. The central question will be whether the specific, confidential formulation in Alkem's ANDA—once revealed in discovery—contains every component in the claimed concentration ranges and exhibits the claimed stability and pH characteristics.
  • A key legal question will be one of claim scope: How will the court construe the functional term "stable"? Will it be defined by the general statements in the specification or limited to the specific quantitative results shown in the patent's examples? The answer to this construction question could determine whether Alkem's stability data for its own product falls within the scope of the claims.