DCT
1:22-cv-00513
Otsuka Pharmaceutical Co Ltd v. Teva Pharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Otsuka Pharmaceutical Co., Ltd. (Japan)
- Defendant: Teva Pharmaceuticals Inc. (Delaware); Teva Pharmaceuticals USA, Inc. (Delaware); Teva Pharmaceutical Industries Ltd. (Israel)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:22-cv-00513, D. Del., 04/22/2022
- Venue Allegations: Venue is alleged to be proper because two Teva defendants are incorporated in Delaware, and the third, an Israeli corporation, may be sued in any judicial district.
- Core Dispute: Plaintiff alleges that Defendants' Abbreviated New Drug Application (ANDA) for generic tolvaptan tablets constitutes an act of infringement of three patents covering pharmaceutical compositions and manufacturing processes for benzazepine compounds.
- Technical Context: The technology concerns formulations and manufacturing methods for tolvaptan, a prescription drug marketed as JYNARQUE® for treating autosomal dominant polycystic kidney disease (ADPKD).
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 216933 with a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed. The complaint was filed within the 45-day statutory window, triggering a 30-month stay of FDA approval for the generic product. The patents are listed in the FDA's Orange Book for JYNARQUE®, which also has orphan drug exclusivity through April 2025.
Case Timeline
| Date | Event |
|---|---|
| 2005-09-02 | Earliest Priority Date for '730 and '735 Patents |
| 2007-06-21 | Earliest Priority Date for '694 Patent |
| 2012-09-25 | U.S. Patent No. 8,273,735 Issued |
| 2013-08-06 | U.S. Patent No. 8,501,730 Issued |
| 2018-04-23 | FDA Approved JYNARQUE® (NDA No. 204441) |
| 2021-02-02 | U.S. Patent No. 10,905,694 Issued |
| 2022-03-08 | Otsuka Received Teva's Notice of Paragraph IV Certification |
| 2022-04-22 | 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 Aug. 6, 2013)
The Invention Explained
- Problem Addressed: The patent describes that prior art methods for synthesizing the subject benzazepine compounds are not suitable for industrial-scale production, as they result in low yield and purity ('730 Patent, col. 2:46-59).
- The Patented Solution: The invention is a product-by-process claim for a "highly pure" form of the benzazepine compound. This high purity is achieved through a specific synthesis process: reducing a precursor compound using a particular class of hydrogenating agents (e.g., sodium borohydride) in a specific molar ratio ('730 Patent, Abstract; col. 13:1-15). This method is designed to avoid the undesirable dehalogenation reactions that occur with other known processes ('730 Patent, col. 13:5-8).
- Technical Importance: The claimed process enables the large-scale, cost-effective manufacturing of a key pharmaceutical intermediate with high purity, a critical requirement for producing a safe and effective commercial drug ('730 Patent, col. 20:41-54).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶44).
- Essential elements of independent claim 1 include:
- 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,
- which is produced by a process comprising reducing a specific precursor compound (formula (1)),
- in the presence of a hydrogenating agent selected from a specific group (lithium aluminum hydride, sodium borohydride, zinc borohydride, and diborane),
- wherein the agent is used in an amount of 0.25 to 1 mole per 1 mole of the precursor compound.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 10,905,694 - "Pharmaceutical Solid Preparation Comprising Benzazepines and Production Method Thereof" (Issued Feb. 2, 2021)
The Invention Explained
- Problem Addressed: The patent's background section explains that the active benzazepine compound has poor solubility, hindering its absorption. While creating an amorphous composite of the drug improves solubility, tablets made directly from this composite fail to disintegrate properly in the gastrointestinal tract, rendering the drug ineffective ('694 Patent, col. 2:30-49).
- The Patented Solution: The invention is a pharmaceutical solid preparation, and a method for making it, that overcomes both problems. It combines an amorphous composite of the drug with a very specific type of disintegrant: "low substituted hydroxypropylcellulose" that must meet precise criteria for its average particle diameter and its 90% cumulative particle diameter ('694 Patent, Abstract; col. 2:50-col. 3:13). This specific formulation is claimed to yield a tablet with both excellent solubility and superior disintegration properties.
- Technical Importance: The invention provides a viable formulation for oral delivery of a poorly soluble drug, ensuring the final tablet product can both dissolve to release the active ingredient and disintegrate effectively for proper absorption ('694 Patent, col. 2:50-66).
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (Compl. ¶54).
- Essential elements of independent claim 1 (a product-by-process claim) include:
- A pharmaceutical solid preparation obtained by a method comprising:
- Step 1: Producing amorphous composites of the drug and hydroxypropylcellulose.
- Step A: Processing a mixture of the amorphous composites, crystalline cellulose, and corn starch/lactose into granules.
- Step 2: Mixing these granules with "low substituted hydroxypropylcellulose," which is further defined as having specific properties (cellulose containing 10-13% hydroxy propoxyl group, average particle diameter of 45-65 µm, and 90% cumulative particle diameter of 150-200 µm).
- Step 3: Processing the final mixture into a solid preparation.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
Multi-Patent Capsule: U.S. Patent No. 8,273,735
- Patent Identification: U.S. Patent No. 8,273,735, "Process for Preparing Benzazepine Compounds or Salts Thereof," issued September 25, 2012.
- Technology Synopsis: Similar to the '730 patent, this patent addresses the need for an improved, industrial-scale process for preparing benzazepine compounds with high yield and purity ('735 Patent, col. 3:26-40). The patent claims specific chemical synthesis processes, such as reacting two precursor compounds in the presence of a carbonylating agent (claim 1) or reducing a precursor using a specific hydrogenating agent (claim 6).
- Asserted Claims: At least claims 6-8 and 10, with 6 and 10 being independent (Compl. ¶63).
- Accused Features: The complaint alleges infringement under 35 U.S.C. § 271(g), asserting that Teva's ANDA products will be manufactured using a process claimed in the '735 patent and subsequently imported into the United States (Compl. ¶¶ 61, 63, 65).
III. The Accused Instrumentality
- Product Identification: The accused instrumentalities are "Teva's ANDA products," defined as generic tolvaptan tablets in 15, 30, 45, 60, and 90 mg dosage forms, for which Teva seeks FDA approval via ANDA No. 216933 (Compl. ¶¶ 2, 35).
- Functionality and Market Context: The accused products are intended to be generic versions of Otsuka's JYNARQUE® tablets and are alleged to be "pharmaceutically and therapeutically equivalent" (Compl. ¶¶ 35, 42, 52). JYNARQUE® is a prescription drug used to slow the decline of kidney function in adults with rapidly progressing autosomal dominant polycystic kidney disease (ADPKD) (Compl. ¶22). The filing of the ANDA signals Teva's intent to market and sell these generic products in the U.S. prior to the expiration of the patents-in-suit (Compl. ¶¶ 35, 40). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint provides a high-level notice of infringement consistent with the requirements for an ANDA action, but does not contain detailed, element-by-element infringement contentions. The analysis below is based on the infringement theories implied by the complaint's allegations against the asserted independent claims.
'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 that Teva's ANDA products are or will be a "highly pure" form of the claimed compound (Compl. ¶¶ 42, 44, 46). | ¶42, ¶44, ¶46 | col. 29:10-15 |
| which is produced by the process which comprises reducing a benzazepine compound of the formula (1)... | The complaint alleges that Teva's ANDA filing seeks approval for a product that is or will be manufactured by a process that includes the claimed reduction step (Compl. ¶¶ 44, 46). | ¶44, ¶46 | col. 29:16-21 |
| in the presence of a hydrogenating agent selected from the group consisting of lithium aluminum hydride, sodium borohydride...and diborane | The complaint alleges that Teva's manufacturing process, as specified in its ANDA, uses a hydrogenating agent from the claimed group (Compl. ¶¶ 44, 46). | ¶44, ¶46 | col. 29:22-27 |
| in an amount of 0.25 to 1 mole per 1 mole of the compound (1). | The complaint alleges that Teva's manufacturing process, as specified in its ANDA, uses the hydrogenating agent in the claimed molar ratio (Compl. ¶¶ 44, 46). | ¶44, ¶46 | col. 29:27-29 |
'694 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical solid preparation obtained by a method, comprising: | The complaint alleges Teva's ANDA products are solid preparations that are or will be made by the claimed method (Compl. ¶¶ 52, 54, 56). | ¶52, ¶54, ¶56 | col. 25:18-19 |
| Step 1 of producing amorphous composites...and (b) hydroxypropylcellulose... | The complaint alleges that Teva's formulation process includes producing an amorphous composite of the drug and hydroxypropylcellulose (Compl. ¶¶ 54, 56). | ¶54, ¶56 | col. 25:20-29 |
| Step A of processing a mixture of (i) the amorphous composites..., (ii) crystalline cellulose, and (iii) corn starch and/or lactose into granules... | The complaint alleges that Teva's formulation process involves granulating the amorphous composite with the specified excipients (Compl. ¶¶ 54, 56). | ¶54, ¶56 | col. 25:30-35 |
| Step 2 of mixing the granules... with (c-1) low substituted hydroxypropylcellulose... [with specific particle size characteristics] | The complaint alleges that Teva's formulation process includes mixing the resulting granules with the specifically defined low substituted hydroxypropylcellulose (Compl. ¶¶ 54, 56). | ¶54, ¶56 | col. 25:36-col. 26:6 |
| Step 3 of processing the mixture obtained in Step 2 into a solid preparation. | The complaint alleges that Teva's process includes a final step of forming the mixture into a solid preparation, such as a tablet (Compl. ¶¶ 54, 56). | ¶54, ¶56 | col. 26:7-11 |
- Identified Points of Contention:
- Factual Questions: A central dispute will concern the details of Teva's manufacturing and formulation processes, which are contained in its confidential ANDA submission. The court will need to compare these confidential specifications against the process steps and material parameters recited in the asserted claims of all three patents.
- Scope Questions (Product-by-Process): For the '730 and '694 patents, a significant legal question arises from the product-by-process claim format. The analysis will question whether infringement requires proof that Teva uses the exact process claimed, or whether infringement can be found if Teva's final product is structurally and functionally identical to a product made by the claimed process, even if Teva's own process differs.
- Technical Questions: The infringement analysis for the '694 patent will raise the technical question of whether the excipients used in Teva's ANDA product meet the highly specific particle size and composition requirements for "low substituted hydroxypropylcellulose" as laid out in claim 1.
V. Key Claim Terms for Construction
Term 1: "highly pure" ('730 Patent, claim 1)
- Context and Importance: This term is a critical limitation that distinguishes the claimed product from prior art. The definition adopted by the court will set the evidentiary bar for infringement. Practitioners may focus on this term because its ambiguity requires judicial construction that could be case-dispositive.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification does not provide a single, explicit definition. A party could argue the term should be understood in a relative sense, meaning simply a higher purity than was achievable with the disclosed prior art methods ('730 Patent, col. 2:46-59).
- Evidence for a Narrower Interpretation: The specification provides specific examples of purity levels achieved, such as "purity 99.1%" and "purity more than 99.5%" ('730 Patent, col. 24:12; col. 13:55-56). A party could argue the term should be construed to require at least these specific numerical purity levels or to mean specifically free from the dehalogenated byproducts mentioned as a problem in the prior art ('730 Patent, col. 13:5-8).
Term 2: "low substituted hydroxypropylcellulose, to obtain a mixture, wherein the low substituted hydroxypropylcellulose is cellulose containing a hydroxy propoxyl group in an amount of about 10 to 13%, has an average particle diameter of 45 to 65 µm, and has a 90% cumulative particle diameter of 150 to 200 µm" ('694 Patent, claim 1)
- Context and Importance: These precise numerical ranges define the novel disintegrant that is the core of the '694 patent's solution. Infringement will hinge on whether Teva's chosen excipient falls within these specific physical and compositional parameters.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim uses the term "about 10 to 13%," which may suggest that some minor deviation from the stated range is permissible. A party might argue that standard industry variance in measurement techniques should be considered.
- Evidence for a Narrower Interpretation: The patent specification and its examples tie the invention's success directly to these specific ranges, contrasting them with other disintegrants that failed ('694 Patent, Table 1). A party would argue that these ranges are not suggestions but are essential, defining features of the invention that must be strictly met.
VI. Other Allegations
- Indirect Infringement: The complaint includes allegations of future active inducement and contributory infringement under 35 U.S.C. § 271(b) and (c) for the '730 and '694 patents, which would occur post-approval (Compl. ¶¶ 46, 56). The factual basis for inducement would likely be Teva's product labeling and instructions, which would direct medical professionals and patients to use the generic drug in an infringing manner.
- Willful Infringement: The complaint does not use the word "willful," but it does allege that Teva has "actual knowledge" of the '730 and '694 patents and "actual and constructive notice" of the '735 patent (Compl. ¶¶ 43, 53, 64). This knowledge is predicated on Teva's Paragraph IV certification letter sent to Otsuka (Compl. ¶37). These allegations, coupled with a prayer for attorney fees in an "exceptional case" (Compl. p. 12, ¶H), lay the groundwork for a claim of willful infringement based on conduct occurring after Teva received notice of the patents.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of process-to-claim mapping: As a factual matter, does the manufacturing and formulation process detailed in Teva's confidential ANDA align with the specific steps, materials, and parameters recited in the asserted claims of the '730, '694, and '735 patents?
- A key legal issue will be the scope of product-by-process claims: Will infringement of the '730 and '694 patents be determined by comparing Teva's final product to Otsuka's, or must Otsuka prove that Teva's actual manufacturing process reads on the claimed method steps?
- The outcome will likely be influenced by claim construction: Can the term "highly pure" in the '730 patent be defined with sufficient precision, and are the specific numerical ranges for the excipient in the '694 patent to be interpreted as strict limits or as allowing for some degree of variance?