DCT

1:21-cv-01682

Bial Portela & Ca Sa Bial Holding SA v. Aurobindo Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:21-cv-01682, D. Del., 11/29/2021
  • Venue Allegations: Venue is asserted in the District of Delaware because Defendant Aurobindo Pharma USA, Inc. is a Delaware corporation.
  • Core Dispute: Plaintiffs allege that Defendant's Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' APTIOM® (eslicarbazepine acetate) tablets constitutes an act of infringement of ten U.S. patents covering the drug's composition, methods of manufacture, and methods of use.
  • Technical Context: The technology relates to eslicarbazepine acetate, a third-generation member of the dibenzazepine family of anticonvulsant drugs used for the treatment of partial-onset seizures in patients with epilepsy.
  • Key Procedural History: This action was commenced under the Hatch-Waxman Act following Plaintiffs' receipt of a "Paragraph IV Certification" notice letter from Aurobindo, dated October 20, 2021, which alleged that the patents-in-suit are invalid, unenforceable, or would not be infringed by Aurobindo's proposed generic product. The filing of the complaint within 45 days of this notice triggers an automatic 30-month stay of FDA approval for Aurobindo's ANDA.

Case Timeline

Date Event
2005-05-06 Earliest Priority Date ('287, '354, '536 Patents)
2006-04-21 Earliest Priority Date ('135, '929 Patents)
2007-10-26 Earliest Priority Date ('431, '244, '781 Patents)
2008-09-13 Earliest Priority Date ('954 Patent)
2011-08-26 Earliest Priority Date ('747 Patent)
2013-02-12 Issue Date: U.S. Patent No. 8,372,431
2013-11-08 FDA approves NDA for APTIOM® as adjunctive therapy
2015-08-27 FDA approves NDA for APTIOM® as monotherapy
2015-12-08 Issue Date: U.S. Patent No. 9,206,135
2017-02-14 Issue Date: U.S. Patent No. 9,566,244
2017-05-09 Issue Date: U.S. Patent No. 9,643,929
2017-09-05 Issue Date: U.S. Patent No. 9,750,747
2017-09-13 FDA approves NDA for APTIOM® for pediatric patients
2017-09-19 Issue Date: U.S. Patent No. 9,763,954
2020-06-09 Issue Date: U.S. Patent No. 10,675,287
2020-06-30 Issue Date: U.S. Patent No. 10,695,354
2020-07-07 Issue Date: U.S. Patent No. 10,702,536
2021-02-09 Issue Date: U.S. Patent No. 10,912,781
2021-10-20 Aurobindo sends Paragraph IV Notice Letter to Plaintiffs
2021-11-29 Complaint Filing Date

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 describes challenges in formulating licarbazepine acetate, an active pharmaceutical ingredient (API) with very low bulk density. This property can lead to poor flowability and compressibility, making it difficult to manufacture uniform tablets, particularly on an industrial scale, and can result in poor dissolution of the final drug product (’431 Patent, col. 5:10-22).
  • The Patented Solution: The invention is a specific solid oral pharmaceutical composition created through a wet granulation process. This process combines the API with a binder (like povidone) and a disintegrant (like croscarmellose sodium) to form granules with improved bulk density and flow properties, enabling consistent tablet manufacturing and reliable drug dissolution (’431 Patent, col. 3:10-24; col. 6:45-56).
  • Technical Importance: Developing a robust, scalable manufacturing process that ensures consistent tablet weight, hardness, and dissolution is critical for regulatory approval and commercial viability of any oral solid dosage drug.

Key Claims at a Glance

The complaint does not identify specific asserted claims. Independent claim 1 is representative and includes the following essential elements:

  • A pharmaceutical composition comprising eslicarbazepine acetate in combination with a binder and a disintegrant.
  • The eslicarbazepine acetate is present in an amount of from 80 to 90 wt %.
  • The binder is present in an amount of from 3 to 10 wt %.
  • The disintegrant is present in an amount of from 3 to 10 wt %.
  • The composition exhibits a dissolution of at least 60% at about 30 minutes at a specified temperature and pH.

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

The Invention Explained

  • Problem Addressed: The patent addresses the challenge of efficiently synthesizing a specific stereoisomer (the (S)-enantiomer or (R)-enantiomer) of a precursor molecule, 10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide, from oxcarbazepine. Traditional methods may produce a mixture of isomers (a racemic mixture), requiring costly and inefficient separation steps, or may use large quantities of expensive and potentially hazardous catalysts and reagents (’135 Patent, col. 2:5-56).
  • The Patented Solution: The invention claims a specific chemical process (an asymmetric catalytic reduction) that uses a particular ruthenium-based catalyst system and controls the reaction's pH to produce the desired (S)- or (R)-enantiomer with high purity and yield. This method is described as being more efficient and economically viable for large-scale manufacturing than prior art processes (’135 Patent, col. 4:3-14; Abstract).
  • Technical Importance: Creating a single, desired stereoisomer of a drug molecule is often crucial, as different isomers can have different therapeutic effects or side effects; an efficient, scalable process to do so is a significant manufacturing advantage.

Key Claims at a Glance

The complaint does not identify specific asserted claims. Independent claim 1 is representative and includes the following essential elements:

  • A process for preparing (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide or its (R)-(-) counterpart.
  • The process involves the reduction of oxcarbazepine.
  • The reduction occurs in the presence of a specific catalyst prepared from [RuX₂(L)]₂ and a specified ligand.
  • The reduction occurs in the presence of a specified hydride source.
  • During the process, the pH is maintained from 6.5 to 8.

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

  • Technology Synopsis: This patent, related to the ’431 Patent, claims a solid oral tablet or capsule consisting of a granular phase and an extragranular phase. It focuses on specific formulations of eslicarbazepine acetate with a super-disintegrant to achieve desired dissolution properties and manufacturing characteristics (Compl. ¶42; ’244 Patent, Abstract).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: The accused features are Aurobindo's proposed generic Eslicarbazepine Acetate tablets, which are alleged to be pharmaceutically equivalent to the commercial APTIOM® product covered by the patent (Compl. ¶106).

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

  • Technology Synopsis: This patent, related to the ’135 Patent, claims a process for preparing eslicarbazepine acetate's active metabolite. The process uses a specific ruthenium catalyst system and a controlled pH environment to achieve a high-purity synthesis of the desired stereoisomer, which is a key step in manufacturing the final drug product (Compl. ¶45; ’929 Patent, Abstract).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: Infringement is alleged based on Aurobindo’s filing of an ANDA for a generic drug, which implies future importation of a product made by a potentially infringing process under 35 U.S.C. § 271(g) (Compl. ¶115, ¶119).

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

  • Technology Synopsis: This patent claims methods of treating various neurological conditions, including epilepsy. It is based on the finding that eslicarbazepine does not aggravate absence seizures, unlike other related drugs, making it particularly suitable for patients susceptible to such seizures (Compl. ¶48; ’747 Patent, col. 1:47-col. 2:4).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: The accused feature is the intended use of Aurobindo's generic product to treat epilepsy, which Plaintiffs allege will be encouraged by the product's label and marketing materials (Compl. ¶131-133).

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

  • Technology Synopsis: This patent claims the therapeutic use of eslicarbazepine for treating intractable epilepsy, a condition where a patient is resistant to other antiepileptic drugs. The invention is based on the discovery that S-licarbazepine is not a substrate for certain drug-efflux transporters (P-gp or MRPs) in the brain, allowing it to be effective where other drugs fail (Compl. ¶51; ’954 Patent, col. 4:9-14).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: The accused feature is the intended use of Aurobindo's generic product to treat epilepsy, which Plaintiffs allege will induce infringement by physicians prescribing it for patients, including those with intractable conditions (Compl. ¶146-148).

U.S. Patent No. 10,675,287 - "Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate"

  • Technology Synopsis: This patent claims a method of treating partial-onset seizures by administering eslicarbazepine acetate once-daily. The invention is based on the unexpected discovery that a once-daily regimen is more efficacious than a twice-daily regimen of the same total dosage, despite the drug's relatively short half-life (Compl. ¶54; ’287 Patent, col. 3:1-12).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: The accused feature is the once-daily use of Aurobindo's generic product for treating seizures, which is the dosing regimen for the branded APTIOM® product and which Plaintiffs allege will be instructed on the generic's label (Compl. ¶57-58, ¶161-163).

U.S. Patent No. 10,695,354 - "Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate"

  • Technology Synopsis: This patent, related to the ’287 Patent, also claims a method of treating partial-onset seizures via a once-daily administration of eslicarbazepine acetate. It specifies a dosage range of about 800 mg to 1800 mg, tying the superior efficacy of the once-daily regimen to specific therapeutic amounts (Compl. ¶59; ’354 Patent, Claim 1).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: The accused feature is the anticipated once-daily administration of Aurobindo's generic product in dosages equivalent to the branded APTIOM® product, as allegedly will be described in the product's prescribing information (Compl. ¶62-63, ¶176-178).

U.S. Patent No. 10,702,536 - "Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate"

  • Technology Synopsis: This patent, also in the same family as the ’287 and ’354 Patents, claims a method of treating partial-onset seizures with once-daily administration of eslicarbazepine acetate. It defines the treatment's efficacy in terms of pharmacokinetic parameters, such as achieving a specific mean maximum plasma concentration (Cmax) of the active metabolite (Compl. ¶64; ’536 Patent, Claim 24).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: The accused feature is the intended once-daily use of Aurobindo's generic product, which is alleged to be bioequivalent to APTIOM® and will therefore produce the claimed pharmacokinetic profile when administered as instructed (Compl. ¶67-68, ¶191-193).

U.S. Patent No. 10,912,781 - "Pharmaceutical Composition Comprising Licarbazepine Acetate"

  • Technology Synopsis: This patent, related to the ’431 and ’244 patents, claims a specific solid oral dosage form of eslicarbazepine acetate with a binder and a disintegrant. It further specifies the composition's apparent density and dissolution profile, reflecting refinements to the formulation for optimal manufacturing and therapeutic performance (Compl. ¶69; ’781 Patent, Abstract, Claim 1).
  • Asserted Claims: The complaint does not specify claims; independent claim 1 is representative.
  • Accused Features: The accused features are Aurobindo's proposed generic Eslicarbazepine Acetate tablets, alleged to be pharmaceutically and therapeutically equivalent to the APTIOM® product and therefore embodying the claimed formulation characteristics (Compl. ¶203).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Aurobindo's proposed generic "Eslicarbazepine Acetate Tablets 200, 400, 600, and 800 mg," for which it seeks FDA approval via ANDA No. 216481 (Compl. ¶11, ¶72).

Functionality and Market Context

The complaint alleges that Aurobindo’s Generic Product is a generic version of Plaintiffs' APTIOM® tablets and has represented to the FDA that its product is "pharmaceutically and therapeutically equivalent" to APTIOM® (Compl. ¶72, ¶80). The product is intended for the treatment of partial-onset seizures in patients four years of age and older (Compl. ¶35, ¶57). As a generic drug, it is intended to be a lower-cost, substitutable alternative to the branded APTIOM® product upon patent expiry or a favorable court ruling.
No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain detailed infringement allegations or claim charts. The infringement counts for each patent are pleaded generally, alleging that the filing of ANDA No. 216481 constitutes technical infringement under 35 U.S.C. § 271(e)(2)(A) and that commercialization after approval will constitute direct and indirect infringement under 35 U.S.C. § 271(a), (b), and (c) (Compl. ¶81-82, ¶92-93). The following claim chart summary is based on the allegations that Aurobindo's product is pharmaceutically equivalent to the product covered by the patent.

'431 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical composition consisting essentially of eslicarbazepine acetate in combination with a binder and a disintegrant... Aurobindo's product is a pharmaceutical composition containing eslicarbazepine acetate and is alleged to be pharmaceutically equivalent to the patented APTIOM® formulation. ¶72, ¶80 col. 15:58-60
wherein the eslicarbazepine acetate is present in an amount of from 80 to 90 wt %... The complaint alleges Aurobindo's product will be sold in dosage forms equivalent to APTIOM®, implying it contains a similar high percentage of the active ingredient. ¶72 col. 16:11-12
the binder is present in an amount of from 3 to 10 wt %... As a pharmaceutically equivalent formulation, Aurobindo's product is alleged to contain a binder within the claimed weight percentage range. ¶80 col. 16:13-14
the disintegrant is present in an amount of from 3 to 10 wt %... As a pharmaceutically equivalent formulation, Aurobindo's product is alleged to contain a disintegrant within the claimed weight percentage range. ¶80 col. 16:15-16
wherein the pharmaceutical composition exhibits a dissolution of at least 60% at about 30 minutes... Aurobindo's product is alleged to be therapeutically equivalent, which requires a comparable dissolution profile to the branded product. ¶80 col. 16:17-22

Identified Points of Contention

  • Scope Questions (Formulation Patents, e.g., ’431): A central question will be whether the specific excipients and their quantities in Aurobindo's formulation fall within the literal scope of the claims. For example, does Aurobindo's chosen binder meet the definition of "povidone," or will Plaintiffs need to assert infringement under the doctrine of equivalents?
  • Technical Questions (Process Patents, e.g., ’135): The primary dispute will be evidentiary. The complaint provides no information on the process Aurobindo uses to synthesize its eslicarbazepine acetate. A key question for the court will be whether discovery reveals that Aurobindo's manufacturing process practices the specific catalytic reduction steps, catalyst systems, and pH controls required by the claims.
  • Functional Questions (Method of Use Patents, e.g., ’287): The analysis will focus on Aurobindo's proposed product label. A key question will be whether the label's instructions for physicians and patients will inevitably lead to administration of the drug in a manner that practices the claimed method (e.g., once-daily dosing for partial-onset seizures), thus establishing Aurobindo's intent to induce infringement.

V. Key Claim Terms for Construction

The complaint does not provide a basis for identifying specific claim construction disputes. However, based on the technology of the lead formulation patent (’431 Patent), the following terms from its independent claims may become focal points.

The Term: "consisting essentially of"

  • Context and Importance: This transitional phrase is legally significant, as it limits the scope of the claim to the specified ingredients (eslicarbazepine acetate, binder, disintegrant) and those that do not materially affect the basic and novel properties of the invention. Practitioners may focus on this term because its construction will determine whether any additional, unlisted excipients in Aurobindo's formulation will allow it to avoid literal infringement.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The use of "consisting essentially of" rather than the more restrictive "consisting of" suggests the claim was not intended to exclude all other components, only those that materially alter the invention's characteristics (’431 Patent, col. 15:58).
    • Evidence for a Narrower Interpretation: The specification's focus on solving problems of flowability and dissolution caused by the API's low bulk density could suggest that any additional excipient that affects these properties would be "material," thereby supporting a narrower construction of what is permitted beyond the listed ingredients (’431 Patent, col. 5:10-18).

The Term: "a binder"

  • Context and Importance: This term's construction will be critical if Aurobindo's formulation uses a binding agent other than the preferred embodiment (povidone) described in the specification. The dispute will be whether "a binder" should be limited to povidone and its close equivalents or read more broadly on any substance that performs a binding function.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claim uses the general term "a binder," not the specific term "povidone," which may suggest the inventors did not intend to limit the claim to a single type of binder (’431 Patent, col. 15:59).
    • Evidence for a Narrower Interpretation: The specification repeatedly highlights povidone as the binder used in the examples and describes its role in the successful wet granulation process. A defendant might argue this emphasis limits the scope of "a binder" to povidone or structurally similar compounds (’431 Patent, col. 6:45-56).

VI. Other Allegations

Indirect Infringement

The complaint alleges both induced and contributory infringement for all asserted patents (Compl. ¶82, ¶93, ¶108). The factual basis for inducement is Aurobindo's alleged knowledge of the patents and its intent for third parties (physicians and patients) to use the generic product in an infringing manner, as instructed by the proposed package insert and other promotional materials (Compl. ¶95-96, ¶132-133). The basis for contributory infringement is the allegation that Aurobindo's product is especially adapted for an infringing use and has no substantial non-infringing use (Compl. ¶84-85, ¶99-100).

Willful Infringement

The complaint does not use the word "willful" but does request an award of costs, expenses, and reasonable attorney fees, declaring the case "exceptional" under 35 U.S.C. § 285 (Compl., Request for Relief ¶F). This allegation is based on Aurobindo's alleged knowledge of the patents-in-suit, as evidenced by their listing in the FDA's Orange Book and by Aurobindo's own Paragraph IV notice letter sent on October 20, 2021 (Compl. ¶97, ¶134).

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

  • A core issue will be one of formulation equivalence: for the composition patents, will discovery show that the specific excipients, quantities, and manufacturing processes used by Aurobindo are identical to those claimed, or will the dispute hinge on whether Aurobindo's formulation, while different, is legally equivalent under the doctrine of equivalents?
  • A second key question will be one of evidentiary proof for process infringement: for the manufacturing patents, what evidence will Plaintiffs be able to obtain regarding Aurobindo's confidential synthesis process, and will that evidence be sufficient to prove that the process meets every limitation of the asserted process claims, particularly the specific catalyst systems and pH controls?
  • A third central question will be one of induced infringement via labeling: for the method-of-use patents, will the FDA-approved label for Aurobindo's generic product be shown to contain instructions that necessarily and intentionally lead physicians and patients to administer the drug in a manner that directly infringes the patented once-daily dosing regimens?