DCT
1:21-cv-08717
Azurity Pharma Inc v. Amneal Pharma LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Azurity Pharmaceuticals, Inc. (Delaware)
- Defendant: Amneal Pharmaceuticals, LLC (Delaware)
- Plaintiff’s Counsel: Saiber LLC
- Case Identification: 1:21-cv-08717, D.N.J., 04/08/2021
- Venue Allegations: Venue is alleged in the District of New Jersey based on Defendant Amneal's principal place of business being located in Bridgewater, New Jersey.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's Katerzia® product constitutes an act of infringement of four patents related to stable oral liquid formulations of amlodipine.
- Technical Context: The technology concerns pharmaceutical formulations of amlodipine, a calcium channel blocker for treating hypertension and coronary artery disease, as a room-temperature-stable oral liquid suspension, which is significant for pediatric, geriatric, or other patients unable to swallow solid tablets.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following a Notice Letter dated February 23, 2021, in which Defendant informed Plaintiff of its filing of ANDA No. 215035 with the U.S. Food and Drug Administration. The patents-in-suit are listed in the FDA's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book") as covering Plaintiff's Katerzia® product (NDA No. 211340).
Case Timeline
| Date | Event |
|---|---|
| 2016-10-07 | Priority Date for ’329, ’039, and ’998 Patents |
| 2018-04-11 | Priority Date for ’453 Patent |
| 2020-06-30 | U.S. Patent No. 10,695,329 Issues |
| 2020-10-13 | U.S. Patent No. 10,799,453 Issues |
| 2021-01-19 | U.S. Patent No. 10,894,039 Issues |
| 2021-02-23 | Defendant Sends Notice Letter of ANDA Filing |
| 2021-03-23 | U.S. Patent No. 10,952,998 Issues |
| 2021-04-08 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,695,329 - "Amlodipine Formulations" (issued Jun. 30, 2020)
The Invention Explained
- Problem Addressed: The patent background describes the difficulty certain patient populations, such as children and the elderly, have with swallowing solid oral dosage forms like tablets (Compl. ¶9; ’329 Patent, col. 9:31-34). Compounding tablets into liquid form by pharmacists can lead to inaccurate dosing, instability, and potential contamination (’329 Patent, col. 9:51-62).
- The Patented Solution: The invention is a stable, oral liquid formulation of amlodipine that does not require refrigeration. The solution involves forming a less soluble salt of amlodipine, amlodipine benzoate, in situ within the liquid formulation. This is achieved by reacting a more water-soluble amlodipine salt, such as amlodipine besylate, with a molar excess of a benzoate salt, like sodium benzoate, to cause the less soluble amlodipine benzoate to precipitate as suspended particles (’329 Patent, Abstract; col. 2:9-22).
- Technical Importance: This approach provides a ready-to-use, room-temperature-stable liquid formulation that facilitates accurate dosing for patients requiring non-standard or variable doses, potentially increasing patient compliance and safety (’329 Patent, col. 9:26-31).
Key Claims at a Glance
- The complaint does not identify specific claims but asserts infringement of the patent generally. Independent claim 1 is the broadest composition claim.
- Independent Claim 1: An oral liquid formulation comprising the following essential elements:
- (i) amlodipine benzoate in an amount corresponding to 1.0 mg/ml amlodipine freebase;
- (ii) 3 mM of a citrate buffer;
- (iii) 0.2 mg/ml to about 10 mg/ml of sodium benzoate;
- (iv) 0.5 mg/ml of silicon dioxide;
- (v) 7.5 mg/ml of hydroxypropyl methylcellulose;
- (vi) 0.15 mg/ml simethicone;
- (vii) 1.0 mg/ml of polysorbate 80; and
- (viii) water;
- wherein the formulation has a pH between 4 and about 6 and is stable under specified conditions.
U.S. Patent No. 10,799,453 - "Amlodipine Formulations" (issued Oct. 13, 2020)
The Invention Explained
- Problem Addressed: The patent addresses the same challenges as its parent, the ’329 Patent: the need for a stable liquid amlodipine formulation to overcome the drawbacks of solid tablets and pharmacist-compounded liquids for certain patient populations (Compl. ¶13; ’453 Patent, col. 17:31-62).
- The Patented Solution: This patent claims a process for producing a suspension of amlodipine benzoate particles with a specific median particle size (D50 value). The process involves creating an aqueous mixture of a soluble amlodipine salt (e.g., besylate), adding a salt-forming agent (e.g., sodium benzoate), and then "subjecting the first mixture to ultrasonic agitation" to precipitate the amlodipine benzoate particles (’453 Patent, Abstract; col. 2:1-6).
- Technical Importance: The use of ultrasonic agitation during the in situ salt formation is intended to control the particle size of the resulting amlodipine benzoate precipitate, leading to a more uniform and physically stable suspension.
Key Claims at a Glance
- The complaint does not identify specific claims. Independent claim 1 is the broadest process claim.
- Independent Claim 1: A suspension comprising amlodipine benzoate particles with a D50 value between about 5 µm and 40 µm, made by a process with these essential elements:
- (i) providing an aqueous mixture comprising amlodipine besylate;
- (ii) adding sodium benzoate to the aqueous mixture to form a first mixture; and
- (iii) subjecting the first mixture to ultrasonic agitation at a frequency between about 20 kHz and 100 kHz, thereby forming a second mixture comprising amlodipine benzoate.
U.S. Patent No. 10,894,039 - "Amlodipine Formulations" (issued Jan. 19, 2021)
- Patent Identification: U.S. Patent No. 10,894,039, "Amlodipine Formulations," issued January 19, 2021 (Compl. ¶17).
- Technology Synopsis: This patent claims a method of treating hypertension in a subject by administering an oral liquid amlodipine formulation. The formulation recited in the claims is substantially similar to the composition claimed in the related ’329 Patent, addressing the same technical problem of providing a stable liquid dosage form (’039 Patent, Abstract; col. 2:42-65).
- Asserted Claims: The complaint asserts the patent generally; Independent Claim 1 is representative.
- Accused Features: The accused feature is the intended use of the Amneal ANDA Product to treat hypertension, as specified on the proposed product label that mirrors the Katerzia® label (Compl. ¶7, ¶28, ¶40-41).
U.S. Patent No. 10,952,998 - "Amlodipine Formulations" (issued Mar. 23, 2021)
- Patent Identification: U.S. Patent No. 10,952,998, "Amlodipine Formulations," issued March 23, 2021 (Compl. ¶21).
- Technology Synopsis: This patent claims a method of treating coronary artery disease (CAD) by administering an oral liquid amlodipine formulation. The patent extends the use of the stable liquid formulation technology, described in the related patents, to a different medical indication (’998 Patent, Abstract; col. 4:41-61).
- Asserted Claims: The complaint asserts the patent generally; Independent Claim 1 is representative.
- Accused Features: The accused feature is the intended use of the Amneal ANDA Product to treat CAD, as Katerzia® is indicated for this use and Amneal's proposed label is alleged to be the same (Compl. ¶7, ¶28, ¶46-47).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is the "Amneal ANDA Product," a generic version of Azurity's Katerzia® oral liquid formulation that is the subject of Amneal's ANDA No. 215035 filed with the FDA (Compl. ¶1, ¶25).
Functionality and Market Context
- The Amneal ANDA Product is an oral liquid suspension of amlodipine intended for use as a calcium channel blocker to treat hypertension and coronary artery disease (Compl. ¶7, ¶28). The complaint alleges that, to secure FDA approval, Amneal's product must have the same active ingredient, dosage form, route of administration, strength, and conditions of use as the branded Katerzia® product, and must be bioequivalent to it (Compl. ¶28). The filing of the ANDA is an artificial act of infringement under 35 U.S.C. § 271(e)(2)(A) that allows for litigation prior to the generic product's market entry (Compl. ¶25, ¶30).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain element-by-element infringement allegations or reference a claim chart. The infringement theory is based on the requirements of the ANDA process: because Defendant's product must be a bioequivalent copy of Plaintiff's Katerzia® product to gain FDA approval, and because Katerzia® is alleged to be covered by the patents-in-suit, the Defendant's product will necessarily infringe (Compl. ¶28, ¶30-31, ¶35-36). The tables below summarize how the complaint's general allegations map to the elements of the representative independent claims.
’329 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| An oral liquid formulation, comprising: (i) amlodipine benzoate in an amount corresponding to 1.0 mg/ml amlodipine freebase; | Defendant's product is alleged to be a generic version of Katerzia® with the same active ingredient and strength. | ¶28, ¶31 | col. 1:67-2:2 |
| (ii) 3 mM of a citrate buffer; | Defendant's product is alleged to have the same dosage form and be bioequivalent to Katerzia®. | ¶28, ¶31 | col. 2:2-3 |
| (iii) 0.2 mg/ml to about 10 mg/ml of sodium benzoate; | Defendant's product is alleged to have the same dosage form and be bioequivalent to Katerzia®. | ¶28, ¶31 | col. 2:3-4 |
| (iv) 0.5 mg/ml of silicon dioxide; | Defendant's product is alleged to have the same dosage form and be bioequivalent to Katerzia®. | ¶28, ¶31 | col. 2:4 |
| (v) 7.5 mg/ml of hydroxypropyl methylcellulose; | Defendant's product is alleged to have the same dosage form and be bioequivalent to Katerzia®. | ¶28, ¶31 | col. 2:5 |
| (vi) 0.15 mg/ml simethicone; | Defendant's product is alleged to have the same dosage form and be bioequivalent to Katerzia®. | ¶28, ¶31 | col. 2:5-6 |
| (vii) 1.0 mg/ml of polysorbate 80; and (viii) water; | Defendant's product is alleged to have the same dosage form and be bioequivalent to Katerzia®. | ¶28, ¶31 | col. 2:6-7 |
| wherein the pH of the formulation is between 4 and about 6... | Defendant's product is alleged to have the same dosage form and be bioequivalent to Katerzia®. | ¶28, ¶31 | col. 2:7-8 |
’453 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A suspension comprising particles comprising amlodipine benzoate and having a median diameter D50 value of between about 5 μm and about 40 μm... | Defendant's product is alleged to be a bioequivalent generic version of Katerzia®, which is allegedly made by the patented process and thus has these properties. | ¶28, ¶36 | col. 3:9-12 |
| ...made by a process comprising: (i) providing an aqueous mixture comprising amlodipine besylate; | Defendant's product is alleged to infringe the patent, implying it is made by the claimed process to achieve bioequivalence. | ¶28, ¶36 | col. 3:13-14 |
| (ii) adding sodium benzoate to the aqueous mixture to form a first mixture; | Defendant's product is alleged to infringe the patent, implying it is made by the claimed process to achieve bioequivalence. | ¶28, ¶36 | col. 3:15-16 |
| (iii) subjecting the first mixture to ultrasonic agitation at a frequency of between about 20 kHz and about 100 kHz... | Defendant's product is alleged to infringe the patent, implying it is made by the claimed process to achieve bioequivalence. | ¶28, ¶36 | col. 3:17-19 |
- Identified Points of Contention:
- Scope Questions: A central issue for the ’329 Patent will be whether Defendant's formulation meets the specific concentrations and components of claim 1. For the ’453 Patent, a key question is whether the term "ultrasonic agitation" can be construed to cover the specific manufacturing process used by the Defendant, the details of which are not yet public.
- Technical Questions: The complaint provides no direct evidence of infringement, relying instead on the regulatory requirement of sameness. A primary technical question will be whether Defendant has successfully "designed around" the patents by, for example, using a different salt of amlodipine, different excipients, or a manufacturing process that avoids "ultrasonic agitation" while still achieving bioequivalence.
V. Key Claim Terms for Construction
The Term: "amlodipine benzoate ... formed in situ" (’329 Patent, claim 2)
Context and Importance: This term is central to the invention's composition claims. The infringement analysis will depend on whether Defendant's ANDA product contains amlodipine benzoate and whether it is created in situ as the patent describes. Practitioners may focus on this term because it defines the core novelty of the formulation.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes the in situ formation as "the reaction of a pharmaceutically acceptable salt of amlodipine that is more soluble in aqueous media than amlodipine benzoate with a molar excess of sodium benzoate" (’329 Patent, col. 2:10-14). This could be argued to cover any process that follows this general reaction scheme.
- Evidence for a Narrower Interpretation: The specification provides specific examples of reacting amlodipine besylate with sodium benzoate (’329 Patent, col. 10:57-67). A defendant may argue that the term should be limited to the specific reactants or reaction conditions disclosed in the preferred embodiments.
The Term: "ultrasonic agitation" (’453 Patent, claim 1)
Context and Importance: This process step is a critical limitation of the asserted process claims in the ’453 Patent. The infringement determination will likely turn on whether Defendant's manufacturing process includes a step that meets the definition of this term.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claims recite a broad frequency range of "between about 20 kHz and about 100 kHz" (’453 Patent, col. 14:48-49). This language could support a construction that covers any use of ultrasound within that range, regardless of the specific equipment (e.g., bath vs. probe) or intensity.
- Evidence for a Narrower Interpretation: A defendant could argue that the term should be interpreted in light of the context provided by the specification, which discusses the goal of producing particles of a certain size (’453 Patent, col. 3:9-12). This might support a construction that requires the agitation to be sufficient to achieve that stated result, potentially narrowing the scope of the term.
VI. Other Allegations
- Indirect Infringement: The complaint alleges that upon FDA approval, Defendant will induce and contribute to infringement of the '039 and '998 method-of-use patents (Compl. ¶42-43, ¶48-49). The alleged basis for inducement is that Defendant's product labeling will instruct physicians and patients to administer the drug for the patented methods (treating hypertension and CAD). The complaint alleges contributory infringement on the basis that the product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶43, ¶49).
- Willful Infringement: The complaint alleges that Defendant had "actual and constructive knowledge" of the ’329 and ’453 patents prior to filing its ANDA, based on their listing in the FDA Orange Book (Compl. ¶32, ¶37). This alleged pre-suit knowledge forms the basis of the request for a finding of willful infringement should the generic product launch.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central factual issue will be one of compositional and process identity: Does Amneal's proposed generic product contain the precise formulation recited in the asserted composition claims, and is it manufactured using the "ultrasonic agitation" process required by the asserted process claims? Resolution will depend on discovery of the confidential details within Amneal's ANDA filing.
- A core legal issue will be one of definitional scope: How will the court construe key claim terms such as "amlodipine benzoate...formed in situ" and "ultrasonic agitation"? The breadth or narrowness of these definitions will be critical in determining whether Amneal’s product, which must be bioequivalent but not necessarily identical in all respects, falls within the scope of the asserted claims.
- An underlying issue for the litigation will be validity: The patents-in-suit will likely face challenges that their claims to specific formulations and processes are obvious in light of prior art related to amlodipine and standard pharmaceutical formulation techniques. The patentee will need to defend the non-obviousness of using in situ precipitation and sonication to solve the specific stability and dosing problems for liquid amlodipine.