DCT

1:18-cv-00279

Bial Portela & Ca SA v. Torrent Pharma Ltd

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-00279, D. Del., 02/16/2018
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Torrent Pharma Inc. is a Delaware corporation.
  • Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' APTIOM® (eslicarbazepine acetate) tablets constitutes an act of infringement of six U.S. patents.
  • Technical Context: The patents relate to pharmaceutical compositions, manufacturing processes, and methods of use for eslicarbazepine acetate, an anticonvulsant drug used to treat partial-onset seizures.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 211227 to the U.S. Food and Drug Administration (FDA). The ANDA included a Paragraph IV certification alleging that Plaintiffs' patents are invalid, unenforceable, and/or will not be infringed by the proposed generic product. Plaintiffs state they received a notice letter regarding this certification on or about January 3, 2018.

Case Timeline

Date Event
2005-07-29 ’135 & ’929 Patents Priority Date
2007-01-15 ’954 Patent Priority Date
2007-10-26 ’431 & ’244 Patents Priority Date
2011-08-26 ’747 Patent Priority Date
2013-02-12 U.S. Patent No. 8,372,431 Issues
2013-11-08 FDA approves NDA for APTIOM® as adjunctive therapy
2015-08-27 FDA approves NDA for APTIOM® as monotherapy
2015-12-08 U.S. Patent No. 9,206,135 Issues
2017-02-14 U.S. Patent No. 9,566,244 Issues
2017-05-09 U.S. Patent No. 9,643,929 Issues
2017-09-05 U.S. Patent No. 9,750,747 Issues
2017-09-13 FDA approves NDA for APTIOM® for pediatric use
2017-09-19 U.S. Patent No. 9,763,954 Issues
2018-01-02 Date of Torrent's Patent Certification Notice Letter
2018-02-16 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 8,372,431 - "Pharmaceutical composition comprising licarbazepine acetate"

  • Issued: February 12, 2013

The Invention Explained

  • Problem Addressed: The patent’s background section describes that the active pharmaceutical ingredient (API), eslicarbazepine acetate, has an "extremely low bulk density" and exhibits "poor flowability." These physical properties make the compound difficult to handle on an industrial scale and challenging to compress into tablets, potentially resulting in very large tablet sizes and poor dissolution characteristics. (’431 Patent, col. 5:4-14).
  • The Patented Solution: The invention claims to solve this problem through a specific pharmaceutical composition formulated using a wet granulation process. This process increases the bulk density of the API mixture from approximately 0.28 g/mL to 0.60 g/mL, which improves its flow and compressibility. The claimed composition consists of specific weight percentages of the API and certain excipients, which enables the creation of a smaller, more consistent, and effective oral dosage form. (’431 Patent, Abstract; col. 3:18-22).
  • Technical Importance: The patented formulation enabled the efficient, large-scale manufacturing of a stable and consistently performing oral tablet for an otherwise difficult-to-formulate anticonvulsant drug. (’431 Patent, col. 4:5-13).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’431 patent (Compl. ¶63). Independent claim 1 is representative of the core composition technology.
  • Independent Claim 1 consists of the following elements:
    • A pharmaceutical composition consisting of:
    • 80-90 wt% eslicarbazepine acetate,
    • 3-10 wt% povidone,
    • 3-10 wt% croscarmellose sodium, and
    • 0.1-3 wt% magnesium stearate.
    • The composition exhibits a dissolution of at least 60% at about 30 minutes at a specified temperature and pH using a standard paddle apparatus.

U.S. Patent No. 9,206,135 - "Asymmetric catalytic reduction of oxcarbazepine"

  • Issued: December 8, 2015

The Invention Explained

  • Problem Addressed: The patent describes prior art methods for synthesizing single-isomer versions of the active drug from its precursor, oxcarbazepine, as inefficient for large-scale production. These prior methods allegedly required high amounts of expensive ruthenium catalysts, which increased costs and resulted in high levels of undesirable metal contaminants in the final product. (’135 Patent, col. 2:8-33).
  • The Patented Solution: The invention discloses an improved manufacturing process that utilizes a specific ruthenium catalyst system while carefully controlling the reaction pH between 6.5 and 8. This method allows for a "greatly reduced quantity of catalyst" and less hydride source, which in turn provides high yields of an "optically pure" product with very low levels of metal contamination. The patent's Figure 1 illustrates the claimed catalytic cycle. (’135 Patent, Abstract; col. 3:4-49; FIG. 1).
  • Technical Importance: This process enabled the cost-effective and industrially scalable synthesis of the active pharmaceutical ingredient to a high degree of purity, a critical factor for obtaining regulatory approval for a pharmaceutical product. (’135 Patent, col. 4:1-10).

Key Claims at a Glance

  • The complaint asserts infringement of "one or more claims" of the ’135 patent (Compl. ¶74). Independent claim 1 is a product-by-process claim defining the final drug substance.
  • Independent Claim 1 consists of the following elements:
    • A compound being (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide,
    • and comprising about 2 ppm of ruthenium or less.

U.S. Patent No. 9,566,244 - "Pharmaceutical composition comprising licarbazepine acetate"

  • Issued: February 14, 2017 (Compl. ¶41).
  • Technology Synopsis: This patent addresses the same manufacturing challenges as the ’431 patent related to the low bulk density of licarbazepine acetate. The invention discloses a pharmaceutical composition made via granulation, where a super-disintegrant is present both within the granules (intragranular) and outside the granules (extragranular) in the final tablet or capsule, a structure intended to optimize both manufacturability and dissolution. (’244 Patent, Abstract; col. 2:1-12).
  • Asserted Claims: Claim 1 (independent). (Compl. ¶89).
  • Accused Features: Torrent's generic Eslicarbazepine Acetate tablet formulation. (Compl. ¶¶85, 87).

U.S. Patent No. 9,643,929 - "Asymmetric catalytic reduction of oxcarbazepine"

  • Issued: May 9, 2017 (Compl. ¶44).
  • Technology Synopsis: Similar to the ’135 patent, this patent claims a method for producing a specific, optically pure form of the active drug metabolite from oxcarbazepine. The process uses a specific catalyst and hydride source under controlled pH conditions to achieve high efficiency and purity, which is described as essential for making the process viable for industrial-scale manufacturing. (’929 Patent, Abstract; col. 2:1-12).
  • Asserted Claims: Claim 1 (independent). (Compl. ¶100).
  • Accused Features: The API in Torrent's generic product and the process used to manufacture it. (Compl. ¶¶96, 98).

U.S. Patent No. 9,750,747 - "Treatments involving eslicarbazepine acetate or eslicarbazepine"

  • Issued: September 5, 2017 (Compl. ¶47).
  • Technology Synopsis: This patent covers a method of treating neurological disorders, such as partial-onset seizures, in patients who are also susceptible to absence seizures. The invention is based on the discovery that eslicarbazepine acetate, unlike structurally related drugs that can aggravate absence seizures, does not have this negative effect and can be used safely in this patient population. (’747 Patent, Abstract; col. 1:50-col. 2:2).
  • Asserted Claims: Claim 1 (independent). (Compl. ¶111).
  • Accused Features: The intended use of Torrent's generic product to treat partial-onset seizures, which the complaint alleges will induce infringement by physicians prescribing it to patients, including those susceptible to absence seizures. (Compl. ¶¶112-114).

U.S. Patent No. 9,763,954 - "Therapeutical uses of eslicarbazepine"

  • Issued: September 19, 2017 (Compl. ¶50).
  • Technology Synopsis: This patent is directed to the therapeutic use of eslicarbazepine, based on the discovery that it is not a substrate for drug-efflux transporters like P-glycoprotein (P-gp). This property is alleged to allow the drug to better penetrate the blood-brain barrier and achieve higher concentrations in the brain, making it particularly effective for treating conditions like pharmacoresistant epilepsy. (’954 Patent, Abstract; col. 4:8-23).
  • Asserted Claims: Claim 1 (independent). (Compl. ¶126).
  • Accused Features: The use of Torrent's generic product to treat epilepsy, which Plaintiffs allege will include treatment of intractable or refractory forms of the condition. (Compl. ¶¶127-129).

III. The Accused Instrumentality

Product Identification

The accused products are Torrent’s Eslicarbazepine Acetate Tablets in 200 mg, 400 mg, 600 mg, and 800 mg dosage forms, for which Torrent seeks FDA approval under ANDA No. 211227 (the "Generic Product"). (Compl. ¶¶11, 53).

Functionality and Market Context

The complaint alleges that Torrent's Generic Product is a generic version of Plaintiffs' APTIOM® tablets and is intended for treating partial-onset seizures. (Compl. ¶¶34, 53). Torrent has represented to the FDA that its product is "pharmaceutically and therapeutically equivalent" to APTIOM®. (Compl. ¶61). The lawsuit was triggered by Torrent's attempt to market this generic product in the United States before the expiration of the patents-in-suit. (Compl. ¶59).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain or append a claim chart. The infringement allegations are based on the premise that Torrent’s filing of ANDA No. 211227, which seeks approval for a product alleged to be therapeutically equivalent to APTIOM®, constitutes a technical act of infringement under 35 U.S.C. § 271(e)(2).

’431 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition consisting of the following: 80-90 wt% eslicarbazepine acetate... Torrent's Generic Product is an eslicarbazepine acetate tablet formulation represented as therapeutically equivalent to APTIOM®. ¶¶53, 61 col. 16:13-14
3-10 wt% povidone, The complaint does not provide specific details of the excipients in Torrent's Generic Product but alleges the final composition will infringe. ¶63 col. 16:14
3-10 wt% croscarmellose sodium, and The complaint does not provide specific details of the excipients in Torrent's Generic Product but alleges the final composition will infringe. ¶63 col. 16:15
0.1-3 wt% magnesium stearate... The complaint does not provide specific details of the excipients in Torrent's Generic Product but alleges the final composition will infringe. ¶63 col. 16:15-16
wherein the composition exhibits a dissolution of at least 60% at about 30 minutes... As a product represented to be therapeutically equivalent, Torrent's Generic Product is expected to have a similar dissolution profile. ¶61 col. 16:16-21

’135 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A compound being (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide... This compound is the active pharmaceutical ingredient in Torrent's Generic Product. ¶¶53, 72 col. 16:50-53
and comprising about 2 ppm of ruthenium or less. The complaint alleges that Torrent's final API will infringe, but provides no specific data on the level of ruthenium contamination. ¶74 col. 16:53-54

Identified Points of Contention

  • Compositional Questions: A primary factual dispute for the ’431 and ’244 patents will concern the precise formulation of Torrent's Generic Product. Key questions include: Does the accused product's formulation contain the exact excipients within the claimed weight-percentage ranges? Does the formulation contain any additional, unlisted excipients that might place it outside the scope of claims using the restrictive "consisting of" language?
  • Purity Questions: For the ’135 and ’929 patents, a central evidentiary question is whether the API in Torrent's Generic Product meets the claimed purity limitation of "about 2 ppm of ruthenium or less." The complaint does not provide factual support for this element, suggesting it will be a focus of discovery.

V. Key Claim Terms for Construction

  • The Term: "consisting of" (from Claim 1 of the ’431 Patent)

  • Context and Importance: This is a closed transitional phrase in patent claiming, meaning the composition must contain the listed ingredients and no others. Its construction is critical because if Torrent's formulation includes any additional excipients not recited in the claim (such as fillers, glidants, or other binders), it may avoid a finding of literal infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The complaint does not provide a basis for analysis of a broader interpretation. Parties seeking one might argue that trace impurities or elements that do not materially alter the invention's characteristics fall outside the exclusionary scope of the term.
    • Evidence for a Narrower Interpretation: The specification of the ’431 Patent provides explicit support for a strict interpretation, stating in one embodiment that "the composition does not contain any filler" and in another that it "does not include a wetting agent." (’431 Patent, col. 3:11-13, col. 3:15-17). This language may be cited to argue that the inventors intended to exclude all other conventional excipients.

  • The Term: "about 2 ppm of ruthenium or less" (from Claim 1 of the ’135 Patent)

  • Context and Importance: The word "about" introduces a degree of numerical flexibility. The scope of this term will determine the precise upper limit of ruthenium contamination that an accused product can have while still infringing the claim. Practitioners may focus on this term because the entire infringement case for this patent could depend on whether Torrent's API falls within the defined range of purity.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: A party could argue that "about" should be interpreted in light of the precision of the analytical instruments used to measure such low concentrations, suggesting a reasonable range of error is encompassed by the term.
    • Evidence for a Narrower Interpretation: The patent specification contrasts the invention with prior art processes that resulted in high, "unacceptable" levels of metal contaminants. (’135 Patent, col. 2:20-27). Further, the patent's examples mention that the resulting product had ruthenium levels "between 5-50 ppm" even after purification steps in one instance and "less than 2 ppm" in another, while noting regulatory guidelines impose a "5 ppm" limit. (’135 Patent, col. 13:38-39; col. 16:13-16). This context may be used to argue that "about 2 ppm" was intended to mean a value very close to 2 ppm and certainly well below the 5 ppm regulatory threshold.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon approval of its ANDA, Torrent will actively induce infringement of the asserted patents. This allegation is based on the claim that Torrent’s proposed package insert and promotional activities will instruct and encourage physicians and patients to use the Generic Product for the patented methods of treatment. (Compl. ¶¶75-78, 112-115). The complaint also alleges contributory infringement for the composition patents, stating the product is especially adapted for an infringing use and has no substantial non-infringing use. (Compl. ¶¶65-66, 91-92).
  • Willful Infringement: The complaint does not make an express allegation of willful infringement. However, it alleges that Torrent has had pre-suit knowledge of the patents-in-suit, citing the "Patent Certification Notice" letter dated January 2, 2018. (Compl. ¶¶78, 115, 130). In its prayer for relief, Plaintiffs request a declaration that this is an "exceptional case" and an award of attorney fees pursuant to 35 U.S.C. § 285. (Compl. Request for Relief F).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A central issue for the composition patents will be one of compositional identity: Does Torrent’s generic formulation, as confidentially described in its ANDA, contain the same ingredients within the same specific weight-percentage ranges as those recited in the claims, particularly given the restrictive "consisting of" language that may preclude any additional excipients?
  • A key evidentiary question for the process and purity patents will be one of factual compliance: Does Torrent's API, as manufactured and supplied for its generic product, contain "about 2 ppm of ruthenium or less," and can Plaintiffs develop sufficient evidence through discovery to prove this asserted fact?
  • The dispute regarding the method-of-use patents will likely turn on the standard for induced infringement: Will Torrent's proposed product label, by seeking an indication for partial-onset seizures generally, be found to contain sufficient instruction or encouragement to physicians to satisfy the specific intent requirement for inducing infringement of claims directed at treating specific patient subpopulations (e.g., those susceptible to absence seizures)?