Bial Portela & Ca SA v. DR Reddy's Laboratories Ltd

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Bial - Portela & Ca Sa. (Portugal), Bial - Holding, SA. (Portugal), and Sunovion Pharmaceuticals Inc. (Delaware)
  • Defendant: DR. Reddy's Laboratories, Ltd. (India) and DR. Reddys Laboratories, Inc. (New Jersey)
  • Plaintiff’s Counsel: McCARTER & ENGLISH, LLP; Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
• Case Identification: 3:18-cv-03098, D.N.J., 03/02/2018
• Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant DR. Reddys Laboratories, Inc. is incorporated in and maintains its principal place of business in New Jersey.
• 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 dispute is in the pharmaceutical sector, concerning drug formulations, chemical synthesis processes, and methods of use for an anticonvulsant drug used to treat epilepsy.
• Key Procedural History: The action was initiated under the Hatch-Waxman Act following Plaintiffs' receipt of a Paragraph IV certification notice letter dated January 17, 2018, in which Defendants challenged the patents-in-suit related to their ANDA No. 211238. The complaint was filed within the 45-day statutory window, triggering a 30-month stay of FDA approval for the generic product.

Case Timeline

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

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

The Invention Explained

• Problem Addressed: The patent's background describes that the active pharmaceutical ingredient (API), eslicarbazepine acetate, possesses an "extremely low bulk density" and poor flowability, making it difficult to handle on an industrial scale and challenging to compress into tablets of a practical size ('431 Patent, col. 5:4-13).
• The Patented Solution: The invention claims to solve this manufacturing problem by using a wet granulation process. This process combines the API with specific excipients, such as a binder (e.g., povidone) and a disintegrant (e.g., croscarmellose sodium), to form granules with a significantly higher bulk density—more than double that of the raw API ('431 Patent, col. 5:26-33). The patent further specifies distributing the disintegrant both within the granules (intragranular) and outside of them (extragranular) to improve tablet dissolution ('431 Patent, col. 2:1-6).
• Technical Importance: The claimed process enabled the large-scale, efficient manufacturing of a stable, consistent oral tablet for a drug that was previously difficult to formulate due to its physical properties ('431 Patent, col. 3:6-14).

Key Claims at a Glance

The complaint does not specify which claims it asserts, but a representative independent claim is Claim 8. Its essential elements are:

• A solid pharmaceutical composition comprising:
• An intragranular phase comprising licarbazepine acetate, povidone, and croscarmellose sodium;
• An extragranular phase comprising croscarmellose sodium and a lubricant;
• Specific weight-percent ranges for licarbazepine acetate (80-90%), povidone (3-10%), croscarmellose sodium (3-10%), and the lubricant (0.1-3%);
• The croscarmellose sodium is "about equally apportioned" between the intragranular and extragranular phases;
• The composition exhibits a specified dissolution profile ('431 Patent, col. 17:19-18:1).

The complaint reserves the right to assert additional claims (Compl. ¶57).

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

The Invention Explained

• Problem Addressed: The patent describes prior art methods for synthesizing the desired single-enantiomer active metabolite from oxcarbazepine as inefficient for large-scale production. These prior methods allegedly required high amounts of an expensive ruthenium catalyst, resulting in a product with undesirable levels of residual metal contamination and making the process economically unviable for industrial manufacturing ('135 Patent, col. 2:8-32).
• The Patented Solution: The invention discloses an improved chemical process for the asymmetric reduction of oxcarbazepine. The core of the solution is the use of a specific ruthenium-based catalyst system in combination with the careful maintenance of the reaction's pH in a narrow range (6.5 to 8) through the controlled addition of a hydride source like formic acid ('135 Patent, col. 3:4-14, col. 7:46-54). This approach allows for a significantly higher substrate-to-catalyst ratio, improving yield, reducing costs, and resulting in a purer final product suitable for pharmaceutical use ('135 Patent, col. 4:1-10).
• Technical Importance: The claimed process provided an economically viable and scalable manufacturing method for producing an optically pure pharmaceutical compound that was previously difficult to synthesize efficiently ('135 Patent, col. 2:56-62).

Key Claims at a Glance

The complaint does not specify which claims it asserts, but a representative independent claim is Claim 1. Its essential elements are:

• A process for preparing (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide;
• The process involves the reduction of oxcarbazepine;
• This reduction occurs in the presence of a specific catalyst prepared from [RuX2(L)]2 and a ligand of formula (A);
• A specified hydride source (e.g., triethylamine and formic acid) is used;
• During the process, a pH from 6.5 to 8 is maintained ('135 Patent, col. 16:47-18:2).

The complaint reserves the right to assert additional claims (Compl. ¶68).

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

• Patent Identification: U.S. Patent No. 9,566,244, “Pharmaceutical composition comprising licarbazepine acetate,” issued February 14, 2017 (Compl. ¶36).
• Technology Synopsis: This patent addresses manufacturing challenges posed by the low bulk density of eslicarbazepine acetate, a problem for creating uniform tablets ('244 Patent, col. 5:4-13). The invention discloses a pharmaceutical composition created through a wet granulation process, which uses a binder and a super-disintegrant (with portions both inside and outside the granules) to yield a formulation with improved density and flow characteristics suitable for industrial-scale tableting ('244 Patent, col. 2:1-11).
• Asserted Claims: The complaint does not specify claims; independent claims include 1.
• Accused Features: DRL’s Generic Product, a tablet formulation alleged to be therapeutically equivalent to APTIOM® and thus to embody the claimed composition (Compl. ¶81, 83).

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

• Patent Identification: U.S. Patent No. 9,643,929, “Asymmetric catalytic reduction of oxcarbazepine,” issued May 9, 2017 (Compl. ¶39).
• Technology Synopsis: This patent discloses an efficient process for manufacturing optically pure eslicarbazepine from its precursor, oxcarbazepine, addressing prior art inefficiencies related to high catalyst cost and product contamination ('929 Patent, col. 2:8-32). The inventive process uses an asymmetric catalytic reduction with a specific ruthenium catalyst system while carefully maintaining the reaction pH between 6.5 and 8, which enables high-yield, high-purity production at an industrial scale ('929 Patent, col. 3:4-14).
• Asserted Claims: The complaint does not specify claims; independent claims include 1.
• Accused Features: The active ingredient in DRL’s Generic Product is alleged to be made by a process that infringes the patent's claims (Compl. ¶94).

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

• Patent Identification: U.S. Patent No. 9,750,747, “Treatments involving eslicarbazepine acetate or eslicarbazepine,” issued September 5, 2017 (Compl. ¶42).
• Technology Synopsis: This patent addresses the clinical problem that certain anticonvulsant drugs in the same chemical class can aggravate absence seizures, a specific type of epileptic event ('747 Patent, col. 1:4-18). The invention claims a method of treating disorders like epilepsy by administering eslicarbazepine acetate or its active metabolite to patients who are susceptible to absence seizures, asserting that these compounds, contrary to expectations, prevent or reduce the incidence of such seizures ('747 Patent, col. 2:50-56).
• Asserted Claims: The complaint does not specify claims; independent claims include 1 and 19.
• Accused Features: DRL’s proposed product labeling is alleged to induce physicians to prescribe its Generic Product for the patented method of use (Compl. ¶106, 108).

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

• Patent Identification: U.S. Patent No. 9,763,954, “Therapeutical uses of eslicarbazepine,” issued September 19, 2017 (Compl. ¶45).
• Technology Synopsis: This patent addresses pharmacoresistant, or "intractable," epilepsy, particularly in patients for whom other drugs like oxcarbazepine are ineffective, which may be due to drug-efflux transporters like P-glycoprotein at the blood-brain barrier ('954 Patent, col. 2:1-12). The invention claims a method for treating this condition by administering eslicarbazepine, which is asserted to be effective because it is not a substrate for these efflux pumps and can therefore achieve therapeutic concentrations in the brain ('954 Patent, col. 4:8-12).
• Asserted Claims: The complaint does not specify claims; independent claims include 1 and 21.
• Accused Features: DRL’s proposed product labeling and promotional activities are alleged to induce physicians to prescribe its Generic Product for treating intractable epilepsy (Compl. ¶121, 122).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "DRL's Generic Product," identified as Eslicarbazepine Acetate Tablets in 200, 400, 600, and 800 mg dosage forms, for which Defendants filed ANDA No. 211238 with the FDA (Compl. ¶11, 48).

Functionality and Market Context

The accused product is a generic version of Plaintiffs' APTIOM® tablets and is intended for treating partial-onset seizures in patients four years of age and older (Compl. ¶29, 48). In its ANDA, Defendant has represented to the FDA that its product is "pharmaceutically and therapeutically equivalent" to the branded APTIOM® product (Compl. ¶55, 66). The filing of the ANDA signifies Defendant's intent to manufacture, market, and sell this generic product in the United States upon receiving FDA approval, prior to the expiration of the patents-in-suit (Compl. ¶48, 58).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

8,372,431 Infringement Allegations

9,206,135 Infringement Allegations

Identified Points of Contention

• Scope Questions: For the method-of-use patents (’747 and ’954), a central question will be whether the specific language in DRL’s proposed product label will be interpreted by a court as actively inducing physicians to prescribe the drug for the patented methods. For example, does the label encourage use in patients with a susceptibility to absence seizures, or does it merely describe a general use for partial-onset seizures that may incidentally overlap?
• Technical Questions: The complaint lacks specific details about DRL’s actual formulation and manufacturing process. A key question for the ’431 and ’244 Patents is whether DRL’s formulation includes a disintegrant that is "about equally apportioned" between the intra- and extra-granular phases. For the ’135 and ’929 Patents, the dispute will turn on whether DRL's confidential manufacturing process for its API uses the specific catalyst system and pH controls claimed in the patents.

V. Key Claim Terms for Construction

The Term: "about equally apportioned" ('431 Patent, Claim 8)

• Context and Importance: This term defines the physical distribution of the disintegrant (croscarmellose sodium) within the tablet formulation. The definition will be critical for determining literal infringement, as Defendant may argue its formulation uses a different distribution that falls outside the claim's scope.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The use of the word "about" suggests the patentee did not intend to be limited to a precise 50/50 split. A party could argue it encompasses any distribution that is functionally similar to a 50/50 split in achieving the desired dissolution.
  • Evidence for a Narrower Interpretation: The specification's examples repeatedly describe the disintegrant as "(1/2 intra-/1/2 extragranular)" ('431 Patent, Examples 6-9), which may suggest that the inventor's concept of "about equally apportioned" was centered on a specific 50/50 division.

The Term: "a pH from 6.5 to 8 is maintained" ('135 Patent, Claim 1)

• Context and Importance: This limitation defines a critical parameter of the claimed chemical manufacturing process. Practitioners may focus on this term because Defendant could seek to avoid infringement by showing its process operates outside this pH range or does not "maintain" it in the manner required.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification describes adding formic acid "as necessary to maintain the pH" ('135 Patent, col. 7:62-65), which could support an interpretation where the pH is allowed to fluctuate as long as it is periodically corrected to stay generally within the 6.5-8.0 range.
  • Evidence for a Narrower Interpretation: The patent emphasizes that "Control of pH is essential" to achieve the invention's benefits of high yield and catalyst efficiency ('135 Patent, col. 7:46-52). A party could argue this requires active and continuous control to keep the pH strictly within the claimed bounds throughout the reaction, not just as an average or target.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement for all six patents. For the method-of-use patents (’747 and ’954), the allegations are based on DRL's future "promotional activities and proposed package insert," which Plaintiffs claim will instruct or encourage physicians and patients to use the generic product in an infringing manner (Compl. ¶107-108, 122-123). For the composition and process patents, inducement is alleged based on DRL's intent to sell a product that embodies the claimed invention or is made by the claimed process (Compl. ¶57, 68).

Willful Infringement

While the complaint does not include a separate count for willful infringement, it alleges that DRL had knowledge of the patents-in-suit as evidenced by its January 17, 2018 Paragraph IV notice letter (Compl. ¶50, 72). The prayer for relief also seeks a declaration that this is an "exceptional case" and an award of attorney fees, which is relief often predicated on a finding of willful infringement or other litigation misconduct (Compl. p. 21, ¶F).

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

• A central factual question will be one of technical identity: Does DRL’s generic formulation and manufacturing process, as detailed in its confidential ANDA, actually replicate the specific compositional percentages, component distributions (e.g., "about equally apportioned"), and process parameters (e.g., "pH from 6.5 to 8 is maintained") required by the asserted composition and process claims?
• A key legal issue will be one of induced infringement: Will the language in DRL’s proposed product label be found to actively encourage or instruct physicians to prescribe the drug for the specific patented methods—treating patients susceptible to absence seizures (’747 Patent) or those with intractable epilepsy previously treated with oxcarbazepine (’954 Patent)—thereby creating liability for infringement?
• A core issue of claim construction will be one of definitional scope: How broadly will the court construe terms of degree like "about equally apportioned" in the formulation patents and process limitations like "maintained" in the synthesis patents, and will DRL's product fall inside or outside those definitions?