DCT
1:20-cv-00786
Bial Portela & Ca SA v. Alkem 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: Alkem Laboratories Limited (India) and S&B Pharma, Inc. (Delaware)
- Plaintiff’s Counsel: Finnegan, Henderson, Farabow, Garrett & Dunner, LLP
- Case Identification: 1:20-cv-00786, D. Del., 07/07/2020
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant S&B Pharma, Inc. is incorporated in the State of Delaware.
- Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs' APTIOM® drug constitutes an act of infringement of three patents related to methods of treating partial-onset seizures.
- Technical Context: The dispute is in the pharmaceutical sector and concerns a specific dosing regimen for eslicarbazepine acetate, an anticonvulsant medication used to treat epilepsy.
- Key Procedural History: The complaint notes that this action follows a prior lawsuit ("First Suit") filed on February 22, 2018, against the same defendants concerning the same ANDA but asserting an earlier set of patents. The patents-in-suit in the current action were all issued in June and July of 2020, shortly before the complaint was filed.
Case Timeline
| Date | Event |
|---|---|
| 2005-05-06 | Priority Date for ’287, ’354, and ’536 Patents |
| 2013-11-08 | FDA approves NDA for APTIOM® as adjunctive therapy |
| 2015-08-27 | FDA approves NDA for APTIOM® as monotherapy |
| 2017-09-13 | FDA approves NDA for APTIOM® for pediatric patients |
| Before 2018-01-08 | Alkem files ANDA No. 211199 |
| 2018-02-22 | Plaintiffs file "First Suit" against Alkem (C.A. No. 18-304) |
| 2020-06-09 | U.S. Patent No. 10,675,287 Issues |
| 2020-06-30 | U.S. Patent No. 10,695,354 Issues |
| 2020-07-07 | U.S. Patent No. 10,702,536 Issues |
| 2020-07-07 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,675,287 - “Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate”
The Invention Explained
- Problem Addressed: The patent’s background section describes that while the drug carbamazepine is commonly used to treat conditions like epilepsy, it can produce toxic metabolites that cause serious side effects. An alternative, oxcarbazepine, was developed to reduce these side effects but has "a greatly reduced potency." (’287 Patent, col. 1:21-34).
- The Patented Solution: The invention is a method of treatment using eslicarbazepine acetate, a compound chemically related to carbamazepine and oxcarbazepine that is intended to avoid toxic metabolites without losing pharmacological activity. The patent discloses the unexpected discovery that administering the drug in a once-daily regimen provides enhanced efficacy compared to administering the same total dosage twice-daily. (’287 Patent, col. 2:64-3:14).
- Technical Importance: A once-daily dosing regimen offers greater convenience over multiple daily doses, which may improve patient compliance and therapeutic outcomes for chronic conditions like epilepsy. (’287 Patent, col. 3:6-14).
Key Claims at a Glance
- The complaint asserts infringement of at least one claim (Compl. ¶66). The first independent claim is Claim 1.
- Claim 1 of the ’287 Patent requires:
- A method for treating a patient with partial-onset seizures
- comprising administering once-daily
- about 1200 mg of eslicarbazepine acetate
- to the patient, wherein the patient is a human
U.S. Patent No. 10,695,354 - “Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate”
The Invention Explained
- Problem Addressed: The patent addresses the same technical problem as the ’287 Patent: the need for an epilepsy treatment that avoids the toxic side effects of carbamazepine while maintaining high potency, a limitation of oxcarbazepine. (’354 Patent, col. 1:21-34).
- The Patented Solution: The invention is a method of using eslicarbazepine acetate, based on the discovery that a once-daily dosing schedule is surprisingly more effective for treating seizures than a twice-daily schedule of the same total amount. (’354 Patent, col. 2:64-3:14).
- Technical Importance: The claimed method provides a more convenient and potentially more effective treatment protocol for epilepsy, which could enhance patient adherence and overall management of the condition. (’354 Patent, col. 3:6-14).
Key Claims at a Glance
- The complaint asserts infringement of at least one claim (Compl. ¶99). The first independent claim is Claim 1.
- Claim 1 of the ’354 Patent requires:
- A method for treating a patient with partial-onset seizures
- comprising administering once-daily
- from about 800 mg to about 1800 mg of eslicarbazepine acetate
- to the patient, wherein the patient is a human
U.S. Patent No. 10,702,536 - "Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate"
The Invention Explained
- The patent addresses the challenge of finding an effective epilepsy therapy with a better safety profile than carbamazepine and higher potency than oxcarbazepine (’536 Patent, col. 1:21-34). The invention is centered on the discovery that a once-daily administration of eslicarbazepine acetate provides an enhanced therapeutic effect for treating partial-onset seizures compared to a twice-daily regimen of the same total dosage (’536 Patent, col. 2:64-3:5).
Key Claims at a Glance
- Asserted Claims: The complaint asserts infringement of at least one claim (Compl. ¶132). The first independent claim is Claim 1.
- Accused Features: The accused feature is the proposed use of Alkem's generic drug for the once-daily treatment of partial-onset seizures, a use that Plaintiffs allege will be instructed by the product's proposed package insert (Compl. ¶55-56, 133-135).
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Alkem's Generic Product," which are Eslicarbazepine Acetate Tablets in 200, 400, 600, and 800 mg dosage forms (Compl. ¶11). Defendants are seeking FDA approval to market this product under Abbreviated New Drug Application (“ANDA”) No. 211199 (Compl. ¶12).
Functionality and Market Context
- The complaint alleges that Alkem's Generic Product is a generic version of Plaintiffs' APTIOM® tablets and is pharmaceutically and therapeutically equivalent (Compl. ¶57, 64). The infringement alleged is not based on the composition of the tablets, but on the future, intended use of the tablets for the treatment of partial-onset seizures, as will allegedly be directed by the product's prescribing information (Compl. ¶13, 43, 49, 55). The act of filing the ANDA to obtain approval for this use before the expiration of the patents-in-suit is the statutory basis for the infringement action under 35 U.S.C. § 271(e)(2) (Compl. ¶13, 65).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that the filing of ANDA No. 211199 is an act of infringement and that the commercial sale of Alkem's Generic Product post-approval would constitute direct and indirect infringement. The core allegation is that Alkem's proposed product label will instruct physicians and patients to administer the drug in a manner that practices the patented methods.
10,675,287 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating a patient with partial-onset seizures | Alkem’s ANDA seeks approval for its generic product for use in treating patients with partial-onset seizures. | ¶13 | col. 1:21-24 |
| comprising administering once-daily | The prescribing information for the reference drug, APTIOM®, instructs once-daily administration, which Alkem’s generic product will allegedly follow. | ¶43, 55 | col. 3:6-9 |
| about 1200 mg of eslicarbazepine acetate | The prescribing information for APTIOM® allegedly instructs administration in a dosage of about 1200 mg. | ¶42-43 | col. 10:55-57 |
| to the patient, wherein the patient is a human. | The ANDA seeks approval for commercial manufacture and sale of the drug for use in human patients in the United States. | ¶13 | col. 1:16-18 |
10,695,354 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for treating a patient with partial-onset seizures | Alkem's ANDA seeks approval for its generic product for treating patients with partial-onset seizures. | ¶13 | col. 1:21-24 |
| comprising administering once-daily | The complaint alleges Alkem's product, like APTIOM®, will be administered once-daily per its instructions. | ¶49, 55 | col. 3:6-9 |
| from about 800 mg to about 1800 mg of eslicarbazepine acetate | The alleged prescribed dosage of about 1200 mg for the reference drug falls within this claimed range. | ¶43, 49 | col. 5:37-40 |
| to the patient, wherein the patient is a human. | The ANDA seeks approval for a product intended for administration to human patients. | ¶13 | col. 1:16-18 |
- Identified Points of Contention:
- Scope Questions: The infringement analysis for the ’287 Patent may raise the question of whether the dosing instructions on Alkem's proposed label will direct administration of "about 1200 mg." The interpretation of "about" could be a central issue. For the ’354 Patent, the analysis will question whether the prescribed doses fall within the broader "from about 800 mg to about 1800 mg" range.
- Technical Questions: In this ANDA context, the primary question is not one of technical operation but of inducement. The case will depend on the specific language of Alkem's proposed (and ultimately approved) package insert. A key question for the court will be whether the label's language actively encourages, recommends, or promotes the performance of all steps of the claimed methods to physicians and patients.
V. Key Claim Terms for Construction
- The Term: "about 1200 mg" (from Claim 1 of the ’287 Patent)
- Context and Importance: The construction of "about" will define the scope of the claim's dosage limitation. Practitioners may focus on this term because Alkem's product is available in 200, 400, 600, and 800 mg tablets, meaning various combinations can be used to achieve doses near, but not exactly, 1200 mg. The term's scope will determine which specific prescribed dosages are covered by the claim.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discloses clinical trials investigating doses "ranging from 400 mg to 2400 mg" and describes a study where doses were increased to 1200 mg, suggesting that the number is a target within a broader therapeutic window, not a rigid requirement (’287 Patent, col. 7:32-34; col. 7:51-53). The use of "about" itself signals an intent to cover values that are approximately 1200 mg.
- Evidence for a Narrower Interpretation: The patent's figures and efficacy data specifically highlight results for a 1200 mg dose, distinguishing it from 400 mg and 800 mg doses (’287 Patent, FIG. 1; col. 10:39-44). A party could argue that "about 1200 mg" should be construed narrowly in light of these specific examples and the quantitative difference in efficacy shown at that level.
VI. Other Allegations
- Indirect Infringement: This is the central theory of the case. The complaint alleges that Alkem will induce infringement by physicians and patients because its proposed package insert and promotional activities will instruct them to use the generic product in a manner that directly infringes the patented methods (i.e., once-daily administration for partial-onset seizures) (Compl. ¶67-69; 100-102; 133-135). The complaint also pleads contributory infringement, alleging Alkem knows its product is especially adapted for an infringing use and is not suitable for a substantial non-infringing use (Compl. ¶72-73; 105-106; 138-139).
- Willful Infringement: The complaint does not contain an explicit allegation of willful infringement. It does, however, allege that Alkem has knowledge of the patents-in-suit, which is a required element for pleading induced infringement (Compl. ¶68; 101; 134).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be one of inducement: will the final, FDA-approved label for Alkem's generic product contain instructions that direct, encourage, or promote the performance of every element of the asserted method claims, or will it contain a "carve-out" that omits the patented method of use?
- A second core issue will be one of claim construction: can the term "about 1200 mg" in the ’287 Patent be construed to cover the range of dosages that will be administered in clinical practice based on Alkem's product and label?
- Finally, an underlying question, though not detailed in the complaint, will be the validity of the patents. In ANDA litigation, the defendant will almost certainly challenge the patents' validity, likely arguing that a once-daily dosing regimen was obvious to try for a person of ordinary skill in the art at the time the invention was made.