DCT
1:20-cv-01094
Azurity Pharma Inc v. Alkem Laboratories Ltd
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Azurity Pharmaceuticals, Inc. (Delaware)
- Defendant: Alkem Laboratories Ltd. (India)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:20-cv-01094, D. Del., 06/21/2021
- Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware based on Defendant’s persistent and continuous business contacts with the state, purposeful availment of its laws, and because the district is a likely destination for the accused product.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s FIRVANQ® product constitutes an act of infringement of three patents directed to stable oral liquid formulations of vancomycin.
- Technical Context: The technology concerns liquid formulations of vancomycin, an antibiotic used to treat bacterial infections such as Clostridium difficile-associated diarrhea, designed to be more stable and palatable than conventionally compounded alternatives.
- Key Procedural History: The litigation was triggered by Defendant’s submission of ANDA No. 214913 to the U.S. Food and Drug Administration (FDA). As required under the Hatch-Waxman Act, Defendant provided Plaintiff with notice letters including a "Paragraph IV Certification," asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic product. The patents are listed in the FDA’s "Orange Book" as covering Plaintiff’s FIRVANQ® product.
Case Timeline
| Date | Event |
|---|---|
| 2014-03-14 | Earliest Priority Date for ’028, ’046, and ’948 Patents |
| 2019-12-03 | U.S. Patent No. 10,493,028 Issues |
| 2020-06-23 | U.S. Patent No. 10,688,046 Issues |
| 2020-07-07 | Date of Defendant’s Notice Letter Regarding the ’028 Patent |
| 2020-07-24 | Date of Defendant’s Notice Letter Regarding the ’046 Patent |
| 2021-03-30 | U.S. Patent No. 10,959,948 Issues |
| 2021-06-21 | Second Amended 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 the antibiotic vancomycin to pediatric and geriatric patients, who often cannot swallow solid oral capsules. The conventional alternative—a pharmacist compounding a liquid from vancomycin powder intended for injection—is described as cumbersome, time-consuming, and resulting in an unflavored, unpalatable solution that is prone to contamination because it lacks preservatives (’028 Patent, col. 5:1-50).
- The Patented Solution: The invention is a non-sterile, stable liquid formulation of vancomycin hydrochloride specifically designed for oral administration. It combines vancomycin with a precise set of excipients, including a buffering agent (citric acid), a sweetener (sucralose), a flavoring agent, a preservative (sodium benzoate), and a dye, to create a solution that is homogenous, palatable, and stable for at least 30 days at both ambient and refrigerated temperatures (’028 Patent, Abstract; col. 2:24-36; col. 3:58-64). This pre-formulated system aims to provide a safer, more consistent, and more convenient alternative to ad-hoc compounding (’028 Patent, col. 6:50-65).
- Technical Importance: The formulation provides a ready-to-use or easy-to-prepare oral liquid antibiotic with a defined shelf life, addressing a need for standardized, safe, and palatable dosing for patient populations unable to use solid dosage forms (’028 Patent, col. 5:1-14).
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims (Compl. ¶45). Independent Claim 1 is representative and includes the following essential elements:
- 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.
- The formulation must be homogenous and stable for at least 30 days at ambient and refrigerated temperatures, have 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 related to the administration of vancomycin, namely the difficulty certain patient populations have with solid dosage forms and the instability and contamination risks of pharmacist-compounded liquids (’046 Patent, col. 5:1-50).
- The Patented Solution: The invention provides a similar non-sterile, stable oral liquid formulation of vancomycin hydrochloride. The formulation includes a specific combination of a buffering agent, a sweetener, a preservative, and a flavoring agent to ensure the final product is homogenous and stable for at least two weeks under ambient and refrigerated conditions, enhancing patient compliance and safety (’046 Patent, Abstract; col. 2:25-48).
- Technical Importance: This formulation provides another specific embodiment of a standardized, stable oral liquid vancomycin, improving upon the safety and convenience of prior methods for patients requiring liquid medication (’046 Patent, col. 6:50-65).
Key Claims at a Glance
- The complaint asserts infringement of one or more unspecified claims (Compl. ¶54). Independent Claim 1 is representative and includes the following essential elements:
- A non-sterile stable liquid formulation for oral administration consisting 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.
- The formulation must be homogenous and stable for at least 2 weeks at ambient and refrigerated temperatures and have a pH of 2.5-4.5.
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 10,959,948 - "Composition and Method for Vancomycin Oral Liquid"
- Patent Identification: U.S. Patent No. 10,959,948, “Composition and Method for Vancomycin Oral Liquid,” issued March 30, 2021.
- Technology Synopsis: This patent, also in the same family, is directed to stable, non-sterile oral liquid formulations of vancomycin hydrochloride. It claims specific combinations of excipients—such as a buffering agent, sweetener, preservative, and flavoring agent—designed to overcome the stability, palatability, and contamination issues associated with traditional compounded vancomycin solutions (’948 Patent, Abstract; col. 2:25-45).
- Asserted Claims: The complaint asserts one or more claims without specificity; Independent Claims 1 and 5 are available for assertion (Compl. ¶63).
- Accused Features: The complaint alleges that Defendant’s ANDA Product, as a proposed generic equivalent to Plaintiff's FIRVANQ®, will infringe the ’948 Patent upon its commercial manufacture, use, or sale (Compl. ¶¶ 62, 64).
III. The Accused Instrumentality
Product Identification
- Defendant Alkem’s proposed generic vancomycin hydrochloride oral solution, identified as the "Alkem ANDA Product" (Compl. ¶32).
Functionality and Market Context
- The complaint describes the accused product as "a kit for oral solution" (Compl. ¶¶ 33, 36). This suggests the product is supplied as a powder and a diluent for reconstitution by a healthcare provider, such as a pharmacist, prior to administration (Compl. ¶¶ 40, 47).
- By filing its ANDA, Alkem has represented to the FDA that its product has the same active ingredients, route of administration, dosage form, strength, and use as Plaintiff's FIRVANQ® product, and is bioequivalent to it (Compl. ¶39). The complaint further alleges that the proposed label for the Alkem ANDA Product is "substantially similar, if not identical," to the label for FIRVANQ® (Compl. ¶41). The product is intended for the U.S. market for treating infections such as C. difficile-associated diarrhea (Compl. ¶¶ 5, 13, 39).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’028 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A non-sterile stable liquid formulation...consisting of: | The Alkem ANDA Product, upon reconstitution as instructed on its proposed label, is alleged to be a liquid formulation containing only the claimed components because it is represented as a generic equivalent of Plaintiff's FIRVANQ® product. | ¶¶39, 47 | col. 4:1-8 |
| (a) 0.1-0.4% w/v anhydrous citric acid, | The reconstituted ANDA product is alleged to contain anhydrous citric acid within the claimed concentration range. | ¶39 | col. 8:41-43 |
| (c) 0.1-0.3% w/v sucralose, | The reconstituted ANDA product is alleged to contain sucralose within the claimed concentration range. | ¶39 | col. 8:15-17 |
| (d) 0.01-0.1% w/v of a flavoring agent, | The reconstituted ANDA product is alleged to contain a flavoring agent within the claimed concentration range. | ¶39 | col. 8:42-49 |
| (e) 0.08-0.2% w/v sodium benzoate, | The reconstituted ANDA product is alleged to contain sodium benzoate within the claimed concentration range. | ¶39 | col. 8:5-11 |
| (f) 0.0001-0.0003% w/v of a dye, and | The reconstituted ANDA product is alleged to contain a dye within the claimed concentration range. | ¶39 | col. 9:5-13 |
| (g) vancomycin hydrochloride...wherein the concentration...is 25-50 mg/ml. | The reconstituted ANDA product is alleged to contain vancomycin hydrochloride at a concentration within the claimed range. | ¶39 | col. 3:15-18 |
| wherein the...formulation is homogenous and stable for at least 30 days...and has a pH of 2.5-4.5. | The reconstituted ANDA product is alleged to meet the claimed stability and pH parameters because it is bioequivalent to Plaintiff's product, which is covered by the patent. | ¶39 | col. 3:58-64 |
’046 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A non-sterile stable liquid formulation...consisting of: | The Alkem ANDA Product, upon reconstitution, is alleged to be a liquid formulation containing only the claimed components because it is represented as a generic equivalent of Plaintiff's FIRVANQ® product. | ¶¶39, 56 | col. 4:1-8 |
| (a) 0.1-0.4% w/v citric acid, | The reconstituted ANDA product is alleged to contain citric acid within the claimed concentration range. | ¶39 | col. 8:41-43 |
| (c) a sweetener that is sucralose, | The reconstituted ANDA product is alleged to contain sucralose as a sweetener. | ¶39 | col. 8:15-17 |
| (d) 0.02-0.08% w/v sodium benzoate, | The reconstituted ANDA product is alleged to contain sodium benzoate within the claimed concentration range. | ¶39 | col. 8:5-11 |
| (e) 20-60 mg/ml vancomycin hydrochloride, and | The reconstituted ANDA product is alleged to contain vancomycin hydrochloride at a concentration within the claimed range. | ¶39 | col. 3:15-18 |
| (f) a flavoring agent. | The reconstituted ANDA product is alleged to contain a flavoring agent. | ¶39 | col. 8:42-49 |
| wherein the...formulation is homogenous and stable for at least 2 weeks...and has a pH of 2.5-4.5. | The reconstituted ANDA product is alleged to meet the claimed stability and pH parameters as a bioequivalent generic of Plaintiff's patented product. | ¶39 | col. 3:58-64 |
Identified Points of Contention
- Scope Questions: The claims are directed to a "liquid formulation," while the accused product is alleged to be a "kit" (Compl. ¶33). A potential issue is whether the act of filing an ANDA for a kit that is reconstituted into an infringing liquid by a third party (a pharmacist) constitutes infringement under 35 U.S.C. § 271(e)(2). The complaint’s allegations of inducement appear tailored to address this issue (Compl. ¶¶ 47, 49).
- Technical Questions: A central question will be one of compositional identity: does Alkem’s ANDA product, once reconstituted, contain every single excipient recited in the claims, within the specified concentration ranges, and nothing more? Defendant’s Paragraph IV certification suggests it may argue non-infringement (Compl. ¶37), which could be based on the use of a different excipient or a concentration outside the claimed ranges. The evidence for this will depend on the contents of Alkem's confidential ANDA filing.
V. Key Claim Terms for Construction
The Term: "consisting of"
- Context and Importance: This transitional phrase appears in the preamble of the asserted independent claims of the ’028 and ’046 patents. In patent law, "consisting of" is a closed-ended term, meaning the claimed formulation must not contain any ingredients other than those explicitly listed, apart from impurities ordinarily associated therewith. The construction of this term is critical because if Alkem’s formulation includes any additional, unlisted excipient (e.g., a different preservative, stabilizer, or sweetener), it would provide a straightforward basis for a non-infringement defense.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term is generally understood to be strictly limiting, leaving little room for a broader interpretation under established case law.
- Evidence for a Narrower Interpretation: The patents repeatedly emphasize the specific combination of listed ingredients as the solution to the technical problem, reinforcing the closed nature of the claims. The summary of the invention in the ’028 Patent, for example, lists a liquid solution comprising specific categories of agents, and Claim 1 recites an even more specific list of those agents (’028 Patent, col. 2:51-57; col. 10:49-65).
The Term: "stable"
- Context and Importance: The claims require the liquid formulation to be "stable" for a defined period (e.g., "at least 30 days" in ’028 Claim 1; "at least 2 weeks" in ’046 Claim 1). The definition of this term will be key to determining infringement. While the FDA requires stability data for product approval, the patent's definition may be different or more specific.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term could be argued to encompass any formulation that remains safe and effective for the specified period, consistent with general pharmaceutical practice.
- Evidence for a Narrower Interpretation: The specification provides a more precise definition, stating that "stable" refers to "vancomycin hydrochloride powder having microbial assay values of greater than 900 or in some embodiments about 1100 µg/mg" and specific compositional percentages of vancomycin B and impurities "at the end of a given storage period" (’028 Patent, col. 9:15-24). A defendant may argue its product does not meet this specific, quantitative definition of stability even if it meets the FDA's regulatory requirements.
VI. Other Allegations
Indirect Infringement
- The complaint alleges that Alkem will induce infringement by third parties (Compl. ¶¶ 49, 58, 67). The factual basis for this allegation is that Alkem's proposed product label will instruct pharmacists or other users to reconstitute the "kit for oral solution," which will allegedly result in the creation of the infringing liquid formulation (Compl. ¶¶ 41, 47, 56, 65).
Willful Infringement
- The complaint does not use the term "willful," but it pleads facts that may support such a claim for post-approval commercial activity. It alleges that Alkem had "actual and constructive knowledge" of the patents prior to its ANDA filing and was aware that the submission constituted an act of infringement (Compl. ¶¶ 48, 57, 66).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of compositional identity: given the claims’ restrictive "consisting of" language, does the formulation detailed in Alkem's confidential ANDA filing contain only the exact excipients listed in the asserted claims, within the specified concentrations, or does it contain any additional or different components that would place it outside the literal scope of the claims?
- A key legal and factual question will be one of infringement by equivalence: since the accused product is supplied as a "kit," the case will turn on whether Alkem’s act of filing an ANDA for a product intended to be reconstituted into the claimed liquid formulation constitutes infringement under 35 U.S.C. § 271(e)(2), particularly through the doctrine of inducement based on the product's proposed label and instructions.