DCT
2:17-cv-02423
Dexcel Pharma Tech Ltd v. Apotex Corp
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Dexcel Pharma Technologies Ltd. and Dexcel Ltd. (Israel)
- Defendant: Apotex Corp. (Delaware) and Apotex Inc. (Canada)
- Plaintiff’s Counsel: Saul Ewing LLP
- Case Identification: 2:17-cv-02423, D.N.J., 04/07/2017
- Venue Allegations: Venue is based on allegations that Defendant Apotex Corp. maintains systematic and continuous contacts with New Jersey, is registered as a drug wholesaler in the state, and has previously submitted to the court's jurisdiction in other matters.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) for a generic version of Omeprazole Delayed Release Tablets constitutes an act of infringement of two patents related to stable pharmaceutical formulations.
- Technical Context: The technology concerns formulations for acid-sensitive proton pump inhibitors like omeprazole, which require protection from stomach acid to be effective, a significant challenge in the large market for heartburn and acid reflux medications.
- Key Procedural History: This is a Hatch-Waxman action triggered by Apotex’s filing of ANDA No. 210070 and its associated Paragraph IV certification, which alleges the patents-in-suit are invalid, unenforceable, or will not be infringed. Plaintiff received notice of the certification on or after February 23, 2017. The complaint also notes related litigation involving the same patents against other ANDA filers.
Case Timeline
| Date | Event |
|---|---|
| 1999-06-22 | Priority Date for ’391 and ’878 Patents |
| 2007-08-14 | U.S. Patent No. 7,255,878 Issued |
| 2015-05-05 | U.S. Patent No. 9,023,391 Issued |
| 2017-02-23 | Plaintiff Received Apotex's Paragraph IV Notice Letter (on or after this date) |
| 2017-04-07 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,023,391 - "Stable Benzimidazole Formulation" (Issued May 5, 2015)
The Invention Explained
- Problem Addressed: The patent addresses the chemical instability of acid-labile drugs like omeprazole. While an enteric coating can protect the drug from stomach acid, the alkaline compounds required in the drug core to stabilize the omeprazole can themselves react with and degrade the conventional acidic enteric coating. This problem was typically solved by adding a separating "subcoating" layer, which complicates and adds expense to the manufacturing process (Compl. Ex. A, ’391 Patent, col. 1:50-62).
- The Patented Solution: The invention claims to solve this problem by eliminating the subcoating layer. This is achieved by preparing the enteric coating material in a solution that has been neutralized to a pH of at least 6.5, making it non-acidic. This neutralized solution can then be applied directly to the alkaline drug core without causing the undesirable degradation reaction during manufacturing or storage (’391 Patent, Abstract; col. 3:11-24).
- Technical Importance: The invention offers a simplified, and therefore potentially more efficient and cost-effective, method for manufacturing a widely used class of oral pharmaceuticals by removing an entire production step. (’391 Patent, col. 2:62-65).
Key Claims at a Glance
- The complaint does not specify which claims it asserts, alleging infringement of "one or more claims" (Compl. ¶37). Independent claim 1 is representative of the patented composition.
- Independent Claim 1 consists essentially of:
- A single tablet core containing a benzimidazole derivative (e.g., omeprazole), sodium stearate as a stabilizer, and at least one non-stabilizing excipient.
- A single enteric polymer layer that is layered directly onto the core.
- The enteric layer is applied from a solution or dispersion having a pH of at least 6.5 and containing a neutralizing agent.
- The right to assert other claims, including dependent claims, is implicitly reserved.
U.S. Patent No. 7,255,878 - "Stable Benzimidazole Formulation" (Issued Aug. 14, 2007)
The Invention Explained
- Problem Addressed: As the parent of the ’391 patent, the ’878 patent addresses the identical technical challenge: the incompatibility between the alkaline-stabilized drug core and the acidic enteric coating in formulations of benzimidazole derivatives, which historically necessitated a separating subcoat (’878 Patent, col. 1:53-2:1).
- The Patented Solution: The patent discloses the same solution as its divisional, the ’391 patent. The core innovation is the direct application of a pH-neutralized enteric coating solution (pH ≥ 6.5) onto the drug-containing substrate, which obviates the need for an intermediate layer by preventing the chemical reaction that would otherwise degrade the coating (’878 Patent, Abstract; col. 3:11-24).
- Technical Importance: The method streamlines the manufacturing of acid-labile drugs by creating a stable final product with fewer, simpler steps. (’878 Patent, col. 2:60-65).
Key Claims at a Glance
- The complaint generically asserts "one or more claims" of the patent (Compl. ¶47). This patent's independent claims (e.g., 1, 12, 23) are directed to methods of production.
- Independent Claim 1 consists essentially of the steps of:
- Forming a substrate with the benzimidazole derivative.
- Preparing a solution of an enteric polymer.
- Neutralizing the polymer solution by adding an alkalizing material.
- Applying a single layer of the neutralized solution directly to the substrate, explicitly "without an intermediate layer."
- The right to assert other claims is implicitly reserved.
III. The Accused Instrumentality
- Product Identification: Apotex’s proposed generic version of Omeprazole Delayed Release Tablets, 20 mg (OTC), which is the subject of Abbreviated New Drug Application (ANDA) No. 210070 submitted to the FDA (Compl. ¶12).
- Functionality and Market Context: The complaint alleges that Apotex's product is a generic equivalent to the plaintiff's existing branded omeprazole product (Compl. ¶12). As a delayed-release tablet, its function is to transport the acid-sensitive omeprazole past the acidic environment of the stomach before releasing the active ingredient. The complaint does not provide specific details regarding the formulation or manufacturing process of the accused product, noting that Apotex has not provided its ANDA for review (Compl. ¶16). The filing of the ANDA itself indicates Apotex's intent to enter the U.S. market for OTC omeprazole upon receiving FDA approval (Compl. ¶12-13).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges infringement based on the filing of the ANDA, asserting on information and belief that the product described therein will meet the limitations of the patents-in-suit. The analysis below is based on these allegations, pending discovery of the actual product formulation and manufacturing process.
'391 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A stable composition for oral administration of a benzimidazole derivative, the composition consisting essentially of: (a) a single tablet core consisting essentially of 1) a benzimidazole derivative | The complaint alleges Apotex's Proposed Product is a generic version of Omeprazole Delayed Release Tablets, which contains the benzimidazole derivative omeprazole. | ¶12, ¶37 | col. 20:20-24 |
| 2) sodium stearate in an amount between about 0.09% to about 4% by weight of the core which is effective to stabilize the benzimidazole derivative in the composition | The complaint alleges infringement on information and belief, which implies the accused product contains the claimed stabilizing agent in the specified concentration. | ¶37 | col. 20:25-29 |
| (b) a single layer comprising an enteric polymer... having been layered directly onto the core from a solution or dispersion having a pH of at least pH 6.5 | The complaint alleges infringement, implying the accused product is a delayed-release tablet that achieves stability using a single, directly-applied enteric coating made from a neutralized solution. | ¶37 | col. 20:33-38 |
'878 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for producing a stable tablet composition for a benzimidazole derivative, the method consisting essentially of: forming a substrate with the benzimidazole derivative | The complaint alleges Apotex will "make" and "use" the accused product, which implies it will be manufactured by a process that begins with forming a substrate containing omeprazole. | ¶47, ¶49 | col. 15:37-41 |
| preparing a solution of an enteric polymer... neutralizing said solution by addition of an alkalizing material | The infringement allegation suggests that Apotex's manufacturing process involves preparing and neutralizing an enteric polymer solution as claimed. | ¶47, ¶49 | col. 15:42-47 |
| applying a single layer of said neutralized solution directly to said substrate, without an intermediate layer | The allegation that Apotex's activities will infringe suggests its manufacturing method uses the key inventive step of applying the neutralized coating as a single layer directly to the core. | ¶47, ¶49 | col. 15:48-51 |
- Identified Points of Contention:
- Evidentiary Question: The central dispute will be factual and can only be resolved through discovery of Apotex's confidential ANDA. The key question is whether the exact formulation and manufacturing process described in the ANDA correspond to the specific elements of the asserted claims, such as the identity and concentration of the stabilizer, the absence of a subcoat, and the pH of the enteric coating solution during application (Compl. ¶16).
- Scope Question: A likely point of contention will be the scope of the phrase "consisting essentially of," used in the claims of both patents. This term allows for the presence of unlisted components so long as they do not materially affect the "basic and novel properties" of the invention—here, a stable, subcoat-less formulation. The case may turn on whether any excipients in Apotex's product, beyond those recited, are found to materially alter this characteristic.
V. Key Claim Terms for Construction
The Term: "consisting essentially of"
- Context and Importance: This transitional phrase, present in the independent claims of both patents, is critical for defining the permissible components of the accused formulation and steps in the accused method. Its construction will determine whether any unlisted ingredients or process variations in Apotex's ANDA place the product outside the scope of the claims.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Parties may argue for the standard legal definition, which would permit unrecited elements that do not materially affect the invention's novel characteristic of achieving stability without a subcoat.
- Evidence for a Narrower Interpretation: The specification repeatedly emphasizes the absence of an intermediate layer as the key feature (’391 Patent, Abstract; col. 2:62-63). A defendant could argue that any unlisted ingredient that serves a purpose analogous to a subcoat, such as physically separating the core and enteric layer or chemically buffering between them, would be a material change falling outside the claim.
The Term: "stabilize" / "stabilizing material"
- Context and Importance: Claim 1 of the ’391 patent requires a core with "sodium stearate... effective to stabilize" the drug and an excipient that is "not a stabilizing material." How "stabilize" is defined is crucial for categorizing the ingredients in Apotex's formulation and determining if it meets these limitations.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent's background describes stability in the context of protecting the drug from acid-driven degradation, suggesting "stabilize" could broadly mean "to reduce degradation." (’391 Patent, col. 1:19-36).
- Evidence for a Narrower Interpretation: The patent teaches using "alkaline constituents" and "basic stabilizing material" to create an alkaline micro-environment for the drug (’391 Patent, col. 1:45-48; col. 6:10-14). A party could argue that "stabilize" should be construed more narrowly to mean only providing alkalinity, and that an agent providing stability via another mechanism (e.g., as an antioxidant) would be a "non-stabilizing material" under the claim.
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement for both patents. The factual basis is the allegation that, upon FDA approval, Apotex will "intentionally encourage" infringement with knowledge of the patents by marketing its product in the United States (Compl. ¶¶40, 50).
- Willful Infringement: While the term "willful" is not used, the complaint alleges the case is "exceptional" and seeks attorneys' fees under 35 U.S.C. § 285 (Compl. ¶¶44, 54). This is predicated on Apotex's alleged knowledge of the patents, for which the complaint points to Apotex's service of its Paragraph IV certification notice as evidence (Compl. ¶15).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue for the court will be one of factual correspondence: Does the specific formulation detailed in Apotex's confidential ANDA—including its excipients, their concentrations, and the number of layers—actually read on the composition claimed in the ’391 patent? Similarly, does its manufacturing method align with the process claimed in the ’878 patent, particularly the direct application of a pH-neutralized coating?
- The case will also likely involve a critical question of claim scope: How will the court construe "consisting essentially of"? The resolution of this issue will define the boundary for infringement, determining whether any differences between the claimed invention and Apotex's product are sufficiently material to place it outside the patents' reach.