DCT
1:18-cv-00972
Otsuka Pharmaceutical Co Ltd v. Alkem Laboratories Ltd
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
- Case Identification: Otsuka Pharmaceutical Co., Ltd. v. Alkem Laboratories Ltd., 1:18-cv-00972, D. Del., 06/29/2018
- Venue Allegations: Venue is asserted under general federal venue statutes, with personal jurisdiction over the foreign defendant based on Federal Rule of Civil Procedure 4(k)(2)(A).
- Core Dispute: Plaintiff alleges that Defendant's filing of an Abbreviated New Drug Application (ANDA) for a generic version of the drug tolvaptan constitutes an act of infringement of a patent directed to a high-purity process for manufacturing the drug's active ingredient.
- Technical Context: The technology concerns chemical synthesis processes for producing tolvaptan (marketed as SAMSCA®), an oral medication used to treat hyponatremia (low blood sodium levels).
- Key Procedural History: This action was filed under the Hatch-Waxman Act, following Defendant's May 16, 2018 notice letter to Plaintiff. The letter included a Paragraph IV Certification asserting that the patent-in-suit is invalid or not infringed by Defendant's proposed generic product. The complaint was filed within the 45-day statutory window, which typically triggers a 30-month stay of FDA approval for the generic drug.
Case Timeline
| Date | Event |
|---|---|
| 2005-09-02 | U.S. Patent No. 8,501,730 Priority Date |
| 2009-05-19 | FDA approves Otsuka's SAMSCA® (tolvaptan) NDA No. 22-275 |
| 2013-08-06 | U.S. Patent No. 8,501,730 Issued |
| 2018-05-16 | Alkem sends Paragraph IV Certification letter to Otsuka |
| 2018-06-29 | 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 patent's background section notes that prior known methods for synthesizing certain benzazepine compounds—useful as intermediates for pharmaceutically active drugs—were "not suitable for producing the desired compounds (1) on industrial scale" (’730 Patent, col. 2:41-43). These prior methods were described as suffering from starting materials that were "hardly obtainable in high yield and in high purity" or processes that could not produce the desired compounds in high yield and purity (’730 Patent, col. 2:45-55).
- The Patented Solution: The invention provides an improved process for preparing these benzazepine intermediates, as well as the final active compounds, in high yield and purity suitable for industrial manufacturing (’730 Patent, col. 3:11-18). The patent describes various reaction schemes, with the asserted claims focusing on a specific reduction step that converts an intermediate ketone (formula 1) into a final hydroxyl compound (formula 10), which is the active ingredient tolvaptan (’730 Patent, Reaction Scheme-IV, col. 12:5-25).
- Technical Importance: The patented process facilitates the efficient, large-scale production of tolvaptan, a nonpeptide vasopressin V2-receptor antagonist used to treat hyponatremia, a condition associated with congestive heart failure and other serious diseases (Compl. ¶14; ’730 Patent, col. 1:63-65).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶26, 31).
- Independent Claim 1 is a product-by-process claim with the following essential elements:
- A product defined as "highly pure 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine," or a salt thereof.
- A specific purity limitation: "having a purity of more than 99.5%."
- A specific manufacturing process step: "which is produced by the process which comprises reducing a benzazepine compound of the formula (1)."
- A specific class of reagents for the process step: "in the presence of a hydrogenating agent selected from the group consisting of lithium aluminum hydride, sodium borohydride, zinc borohydride, and diborane."
- A specific quantity of the reagent: "in an amount of 0.25 to 1 mole per 1 mole of the compound (1)."
- The complaint does not assert specific dependent claims but may reserve the right to do so.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendant Alkem's generic tolvaptan tablets (15, 30, and 60 mg) for which it seeks FDA approval via ANDA No. 211891 (Compl. ¶4).
Functionality and Market Context
- The accused product is intended to be a generic equivalent of Plaintiff's SAMSCA® product, an oral medication for treating hyponatremia in adults (Compl. ¶14-15). The infringement allegation is not based on the tablet's therapeutic use but on the process by which Alkem allegedly manufactures the active pharmaceutical ingredient (API), tolvaptan, which is then formulated into the final tablet form (Compl. ¶26). Alkem seeks to market its ANDA product as a lower-cost generic alternative to SAMSCA® upon receiving FDA approval (Compl. ¶16).
IV. Analysis of Infringement Allegations
The complaint alleges that Alkem's ANDA product will infringe Claim 1 of the ’730 patent, either literally or under the doctrine of equivalents (Compl. ¶26). As this is a product-by-process claim, infringement analysis requires evaluating both the final product and the process used to make it. The complaint does not provide a claim chart or specific factual allegations detailing Alkem's manufacturing process. No probative visual evidence provided in complaint.
'730 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A highly pure 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine... or a salt thereof | The complaint alleges on information and belief that Alkem's ANDA product is or contains this specific chemical compound, tolvaptan (Compl. ¶4). | ¶26 | col. 29:8-13 |
| having a purity of more than 99.5% | The complaint alleges that the tolvaptan in Alkem's ANDA product meets this purity threshold. | ¶26 | col. 29:11-12 |
| which is produced by the process which comprises reducing a benzazepine compound of the formula (1) | The complaint alleges on information and belief that Alkem's manufacturing process includes the step of reducing the specified benzazepine ketone intermediate to produce tolvaptan. | ¶26 | col. 29:13-15 |
| in the presence of a hydrogenating agent selected from the group consisting of lithium aluminum hydride, sodium borohydride, zinc borohydride, and diborane | The complaint alleges on information and belief that Alkem's reduction process utilizes one of the four specifically enumerated hydrogenating agents. | ¶26 | col. 29:25-29 |
| in an amount of 0.25 to 1 mole per 1 mole of the compound (1) | The complaint alleges on information and belief that Alkem's process uses the hydrogenating agent in a quantity that falls within the claimed molar ratio. | ¶26 | col. 29:29-31 |
- Identified Points of Contention:
- Evidentiary Question: A primary issue will be whether Plaintiff can obtain evidence through discovery of Alkem’s confidential ANDA to substantiate its "information and belief" allegations. The complaint lacks any specific facts suggesting that Alkem's proprietary manufacturing process uses the claimed reduction step, reagents, and molar ratios.
- Scope Question (Product-by-Process): The case will likely center on the product-by-process nature of Claim 1. Alkem's Paragraph IV letter suggests a non-infringement defense (Compl. ¶17), which may be based on the use of a different, "design-around" manufacturing process. A key legal and factual question will be whether Otsuka can prove that Alkem’s process is the same as the one claimed, as is generally required to prove infringement of a product-by-process claim.
V. Key Claim Terms for Construction
The Term: "highly pure"
Context and Importance: This term appears at the outset of Claim 1 and describes the resulting product. Practitioners may focus on this term because, as a qualitative descriptor, its meaning could be debated. Its construction is important for defining the scope of the claimed product itself.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent repeatedly describes the invention's purpose as producing compounds in "high yield and high purity on industrial scale" (’730 Patent, col. 3:15-18), suggesting the term may be interpreted in the context of what is considered high purity for an industrial pharmaceutical process.
- Evidence for a Narrower Interpretation: Claim 1 itself immediately follows "highly pure" with the quantitative limitation "having a purity of more than 99.5%" (’730 Patent, col. 29:11-12). A party could argue that "highly pure" is defined by, and is coextensive with, this explicit numerical floor, or is otherwise rendered redundant by it.
The Term: "reducing a benzazepine compound of the formula (1)"
Context and Importance: This phrase recites the core chemical transformation of the claimed process. The dispute is less likely to be about the chemical meaning of "reducing" and more about whether Alkem's process, in fact, performs this exact step on this exact starting material. The patent specification illustrates this step in Reaction Scheme-IV, showing the conversion of a ketone to a hydroxyl group (’730 Patent, col. 12:5-25).
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The term "reducing" is a standard chemical term, and a party might argue it should be given its plain and ordinary meaning to one of skill in the art, encompassing any reaction that achieves the specified transformation.
- Evidence for a Narrower Interpretation: A party might argue the term should be limited to the specific context of the examples provided, such as the use of sodium borohydride in methanol as a reducing system (’730 Patent, col. 24:1-10).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Alkem's future manufacture, use, and sale of its ANDA product will induce or contribute to the infringement of Claim 1 (Compl. ¶31). The factual basis for the required knowledge and intent for these claims appears to be Alkem's pre-suit awareness of the ’730 patent, as demonstrated by its Paragraph IV Certification letter (Compl. ¶18).
- Willful Infringement: The complaint does not use the word "willful" but requests a declaration that the case is "exceptional" under 35 U.S.C. § 285, which allows for an award of attorney fees (Prayer for Relief D). This allegation is likely predicated on Alkem’s pre-suit knowledge of the patent and its decision to nonetheless proceed with seeking FDA approval for its generic product (Compl. ¶18).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of evidentiary proof: Can Otsuka, through discovery of Alkem’s confidential ANDA, demonstrate that Alkem's manufacturing process for tolvaptan literally practices every step of the process recited in Claim 1, including the choice of reagent and its specific molar ratio? The outcome of the case may depend entirely on the contents of Alkem's proprietary process documents.
- The case will also turn on the question of non-infringing alternatives: Given the product-by-process format of the asserted claim, a key question will be whether Alkem has successfully developed a "design-around" synthesis. The court will need to determine if Alkem's process for making a chemically identical and equally pure product is sufficiently different from the patented method to be non-infringing.