DCT
1:25-cv-00318
Otsuka Pharmaceutical Co Ltd v. Alkem Laboratories Ltd
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Otsuka Pharmaceutical Co., Ltd. (Japan)
- Defendant: Alkem Laboratories Ltd. (India)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Venable LLP
- Case Identification: 1:25-cv-00318, D. Del., 03/13/2025
- Venue Allegations: Venue is asserted based on Defendant being an alien corporation subject to suit in any judicial district, and alternatively, on Defendant’s intent to market and sell its products in Delaware.
- Core Dispute: Plaintiff alleges that Defendant’s Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff’s JYNARQUE® (tolvaptan) tablets constitutes an act of infringement of three U.S. patents covering pharmaceutical formulations and manufacturing processes.
- Technical Context: The technology concerns formulations and manufacturing methods for tolvaptan, a treatment for autosomal dominant polycystic kidney disease (ADPKD), designed to overcome the drug's poor solubility and ensure consistent bioavailability.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 220147 with a Paragraph IV certification. Plaintiff received Defendant's notice letter on January 30, 2025, and filed this complaint within the 45-day statutory window, triggering a 30-month stay on FDA approval of the generic product. Plaintiff’s drug, JYNARQUE®, is noted to have orphan drug exclusivity until April 23, 2025.
Case Timeline
| Date | Event |
|---|---|
| 2005-09-02 | Earliest Priority Date for ’735 and ’730 Patents |
| 2007-06-21 | Earliest Priority Date for ’694 Patent |
| 2012-09-25 | ’735 Patent Issued |
| 2013-08-06 | ’730 Patent Issued |
| 2018-04-23 | FDA Approved NDA for JYNARQUE® Tablets |
| 2021-02-02 | ’694 Patent Issued |
| 2025-01-30 | Defendant Sent Paragraph IV Notice Letter to Plaintiff |
| 2025-03-13 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,501,730 - "Process for Preparing Benzazepine Compounds or Salts Thereof," issued August 6, 2013
The Invention Explained
- Problem Addressed: The complaint does not provide the patent, but its related U.S. Patent No. 8,273,735 indicates that prior art methods for synthesizing the subject benzazepine compounds were not suitable for industrial-scale production, suffering from low yield and purity (U.S. 8,273,735, col. 2:50-58).
- The Patented Solution: The complaint states the patent claims "compositions made by processes for preparing novel benzazepine compounds" (Compl. ¶19). Based on the related '735 patent, this likely involves a novel synthesis pathway that provides the desired compounds and their intermediates in high yield and purity, making the process commercially viable for large-scale manufacturing (U.S. 8,273,735, Abstract).
- Technical Importance: The invention provided a method to produce a pharmaceutically important class of compounds at an industrial scale, which was not feasible with prior art techniques.
Key Claims at a Glance
- The complaint asserts infringement of "at least claim 1" (Compl. ¶39).
- The complaint does not provide the language of the asserted claim(s).
- The complaint reserves the right to assert other claims (Compl. ¶39, "one or more claims").
U.S. Patent No. 10,905,694 - "Pharmaceutical Solid Preparation Comprising Benzazepines and Production Method Thereof," issued February 2, 2021
The Invention Explained
- Problem Addressed: The patent discloses that the active benzazepine compound has poor solubility, which hinders its absorption in the gastrointestinal tract. While creating an amorphous composite of the drug improves solubility, directly compressing this composite into a tablet results in a pill that fails to disintegrate, preventing the drug's release and leading to inconsistent pharmacological activity (’694 Patent, col. 1:30-34, col. 2:38-49).
- The Patented Solution: The invention is a pharmaceutical solid preparation, and a method for making it, that solves the dual challenge of solubility and disintegration. The solution involves first creating an amorphous composite of the drug and hydroxypropylcellulose, granulating it with other excipients, and then mixing those granules with a specific disintegrant—"low substituted hydroxypropylcellulose" having a defined particle size distribution—before final processing into a tablet (’694 Patent, Abstract; col. 2:58-65).
- Technical Importance: This formulation technology enables the creation of a stable, effective oral dosage form for a poorly soluble active ingredient by ensuring both its dissolution and its release via tablet disintegration.
Key Claims at a Glance
- The complaint asserts infringement of "at least claim 1" (Compl. ¶49).
- The essential elements of independent claim 1, a product-by-process claim, include:
- A first step of producing amorphous composites of the benzazepine drug and hydroxypropylcellulose.
- A granulation step (Step A) processing the amorphous composites with crystalline cellulose and corn starch and/or lactose.
- A mixing step (Step 2) combining the granules with a specific low substituted hydroxypropylcellulose (defined by hydroxy propoxyl content and particle diameter).
- A final processing step (Step 3) to form the solid preparation.
- The complaint reserves the right to assert other claims (Compl. ¶49, "one or more claims").
U.S. Patent No. 8,273,735 - "Process for Preparing Benzazepine Compounds or Salts Thereof," issued September 25, 2012
- Technology Synopsis: The patent addresses the challenge that prior methods for manufacturing certain benzazepine compounds were not suitable for industrial scale due to issues with yield and purity (’735 Patent, col. 2:50-58). The invention provides a novel chemical process that produces these compounds and their intermediates at a high yield and purity, enabling efficient, large-scale manufacturing (’735 Patent, Abstract).
- Asserted Claims: Claims 6-8 and 10 (Compl. ¶58).
- Accused Features: The complaint seeks a declaratory judgment that the future importation, sale, or use of Alkem's ANDA products will infringe the asserted claims, alleging that these products are made by the patented process (Compl. ¶56, ¶58).
III. The Accused Instrumentality
Product Identification
- Alkem's tolvaptan tablets in 15, 30, 45, 60, and 90 mg dosage forms, for which Alkem seeks FDA approval via ANDA No. 220147 (Compl. ¶2).
Functionality and Market Context
- The accused products are proposed generic versions of Otsuka’s JYNARQUE® tablets, which are prescription drugs used to slow the decline of kidney function in adults with autosomal dominant polycystic kidney disease (ADPKD) (Compl. ¶17, ¶30). The complaint states that Alkem has represented to the FDA that its products are "pharmaceutically and therapeutically equivalent" to JYNARQUE® tablets (Compl. ¶37, ¶47).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
'730 Patent Infringement Allegations
The complaint does not provide the language of the asserted claim(s) or any specific factual allegations mapping the accused product or its manufacturing process to the elements of any claim. The infringement allegation is made on "information and belief" without supporting detail (Compl. ¶39). Therefore, a detailed analysis is not possible based on the complaint.
'694 Patent Infringement Allegations
The complaint alleges infringement based on the submission of the ANDA, asserting that the resulting product will infringe, but does not contain a claim chart. The infringement theory appears to be that because Alkem’s product is represented as "pharmaceutically and therapeutically equivalent" to JYNARQUE®, its manufacturing process must meet the limitations of the asserted product-by-process claim (Compl. ¶47, ¶49).
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical solid preparation obtained by a method, comprising: Step 1 of producing amorphous composites consisting of (a) 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzo-azepine...and (b) hydroxypropylcellulose... | Based on the allegation of therapeutic equivalence, Alkem's manufacturing process is alleged to begin by creating an amorphous composite of the active ingredient (tolvaptan) and hydroxypropylcellulose. | ¶47, ¶49 | col. 26:19-25 |
| Step A of processing a mixture of (i) the amorphous composites obtained in Step 1, (ii) crystalline cellulose, and (iii) corn starch and/or lactose into granules using a granulation method; | Alkem's process is alleged to include a granulation step that combines the amorphous composite with crystalline cellulose and either corn starch or lactose. | ¶47, ¶49 | col. 26:26-30 |
| Step 2 of mixing the granules obtained in Step A with (c-1) low substituted hydroxypropylcellulose...wherein the low substituted hydroxypropylcellulose...has an average particle diameter of 45 to 65 µm, and has a 90% cumulative particle diameter of 150 to 200 µm... | Alkem's process is alleged to include mixing the granules with a specific type of low substituted hydroxypropylcellulose that meets the claim's narrowly defined particle size distribution. | ¶47, ¶49 | col. 26:31-39 |
| and Step 3 of processing the mixture obtained in Step 2 into a solid preparation... | Alkem's process is alleged to conclude by forming the final solid dosage form (tablets) from the mixture. | ¶2, ¶49 | col. 26:40-42 |
- Identified Points of Contention:
- Evidentiary Question: The complaint's infringement theory for the product-by-process claim rests on an inference from Alkem's "therapeutic equivalence" certification. A central question will be what evidence Otsuka can obtain in discovery to prove that Alkem’s actual manufacturing process uses every ingredient and performs every step as required by the claim.
- Technical Question: A likely point of dispute will be whether the disintegrant used by Alkem meets the specific numerical limitations for "average particle diameter" and "90% cumulative particle diameter" recited in claim 1 for the "low substituted hydroxypropylcellulose."
V. Key Claim Terms for Construction
'694 Patent
- The Term: "low substituted hydroxypropylcellulose"
- Context and Importance: This term defines the key disintegrant that the inventors used to solve the technical problem of the tablet failing to break apart. Claim 1 further defines the term with specific numerical ranges for its physical properties. The construction of this term, and whether it is limited to the specific parameters in the claim, will be dispositive for the infringement analysis.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a general definition of the term as "cellulose containing a hydroxy propoxyl group in an amount of about 5 to 16 wt. %" (’694 Patent, col. 6:64-66). A party might argue for this broader definition, detached from the specific particle sizes mentioned elsewhere.
- Evidence for a Narrower Interpretation: Claim 1 itself explicitly narrows the term, requiring it to have "an average particle diameter of 45 to 65 µm, and...a 90% cumulative particle diameter of 150 to 200 µm" (’694 Patent, col. 26:36-39). The abstract and working examples also highlight the importance of specific grades and particle sizes, suggesting these limitations are essential to the invention (’694 Patent, Abstract; Table 1).
VI. Other Allegations
- Indirect Infringement: The complaint includes allegations of active inducement (§ 271(b)) and contributory infringement (§ 271(c)) for the '730 and '694 patents (Compl. ¶41, ¶51). These allegations are based on the premise that if Alkem's ANDA is approved, it will market the product for infringing uses, thereby inducing infringement by physicians and patients.
- Willful Infringement: While the complaint does not use the word "willful," it lays a foundation for such a claim by alleging that Alkem has "actual knowledge" of the patents-in-suit, in part from receiving Otsuka's Paragraph IV notice letter (Compl. ¶32, ¶38, ¶48, ¶59).
VII. Analyst’s Conclusion: Key Questions for the Case
A primary issue will be one of evidentiary proof: For the process and product-by-process claims across all three patents, can Otsuka establish through discovery that Alkem's confidential manufacturing process mirrors the specific steps and components recited in the asserted claims? The complaint’s initial reliance on regulatory equivalence is a pleading posture, not a substitute for factual evidence of the accused process.
A second key issue will be one of claim scope: For the '694 patent, the infringement analysis will likely turn on the construction of "low substituted hydroxypropylcellulose." The court's decision on whether this term is strictly limited by the explicit particle size and chemical composition parameters recited in Claim 1 will be critical in determining whether Alkem's product, which may use a different disintegrant, falls within the scope of the patent.