DCT
1:20-cv-00782
Bial Portela & Ca SA v. Lupin Ltd
Key Events
Amended Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bial - Portela & Ca Sa. (Portugal), Bial - Holding, SA. (Portugal), and Sunovion Pharmaceuticals Inc. (Delaware)
- Defendant: Lupin Limited (India) and Lupin Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Ashby & Geddes; Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:20-cv-00782, D. Del., 07/07/2020
- Venue Allegations: Venue is alleged to be proper as Defendant Lupin Pharmaceuticals, Inc. is incorporated in the State of Delaware.
- Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the epilepsy drug APTIOM® constitutes an act of infringement of three U.S. patents covering methods of treating partial-onset seizures.
- Technical Context: The technology relates to pharmaceutical methods of use, specifically the administration of eslicarbazepine acetate in a once-daily dosing regimen to treat epilepsy.
- Key Procedural History: The complaint notes that Plaintiffs previously filed a separate lawsuit (C.A. No. 18-312-CFC) against the same defendants concerning the same ANDA, but asserting a different set of patents. This subsequent litigation targets newly issued patents, suggesting an ongoing effort by the brand manufacturer to protect its APTIOM® franchise.
Case Timeline
| Date | Event |
|---|---|
| 2005-05-06 | Earliest Patent Priority Date ('287, '354, '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 |
| 2018-01-09 | Date of Lupin's Notice Letter to Plaintiffs |
| 2018-02-23 | Plaintiffs file "First Suit" against Lupin (18-312-CFC) |
| 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 carbamazepine is a common treatment for conditions like epilepsy, it can produce toxic metabolites that cause serious side effects, and a related compound, oxcarbazepine, has "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 that is believed to avoid certain toxic metabolites without losing pharmacological activity (’287 Patent, col. 1:46-54). The patent discloses the unexpected discovery that administering the drug in a once-daily regimen provides enhanced efficacy and a greater systemic exposure to the active metabolite compared to administering the same total daily dose in a twice-daily regimen (’287 Patent, col. 2:63-col. 3:12, col. 15:1-10).
- Technical Importance: This discovery suggests a more convenient and potentially more effective dosing schedule for patients, which is a significant factor in managing chronic conditions like epilepsy.
Key Claims at a Glance
- The complaint asserts infringement of at least one claim without specifying which (’287 Patent; Compl. ¶67). Independent claim 1 is representative:
- 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.
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 10,695,354 - Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate
The Invention Explained
- Problem Addressed: The technology described in the ’354 Patent is identical to that of the ’287 Patent, addressing the need for an epilepsy treatment with the efficacy of carbamazepine but with a more favorable side-effect profile (’354 Patent, col. 1:21-34).
- The Patented Solution: The ’354 Patent also discloses the method of using eslicarbazepine acetate and is based on the same discovery that a once-daily dosing regimen is unexpectedly more effective than a twice-daily regimen (’354 Patent, col. 2:63-col. 3:12).
- Technical Importance: As with the ’287 Patent, the claimed invention offers the potential for improved patient convenience and therapeutic outcomes.
Key Claims at a Glance
- The complaint asserts infringement of at least one claim without specification (’354 Patent; Compl. ¶100). Independent claim 1 is representative:
- 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.
- The complaint does not explicitly reserve the right to assert dependent claims.
U.S. Patent No. 10,702,536 - Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate
- Multi-Patent Capsule
- Patent Identification: U.S. Patent No. 10,702,536, “Methods of Treatment of Partial Onset Seizures Using Eslicarbazepine Acetate,” issued July 7, 2020.
- Technology Synopsis: This patent is part of the same family as the ’287 and ’354 patents. It is also directed to methods of treating partial-onset seizures based on the unexpected efficacy of a once-daily dosing regimen of eslicarbazepine acetate (’536 Patent, Abstract, col. 2:63-col. 3:5).
- Asserted Claims: The complaint asserts at least one unspecified claim of the ’536 patent (Compl. ¶133). Independent claim 1 is representative.
- Accused Features: The complaint alleges that the proposed use of Lupin's generic product, as will be described in its package insert, will involve once-daily administration for treating partial-onset seizures, thereby infringing the claims (Compl. ¶¶133-135).
III. The Accused Instrumentality
Product Identification
- Lupin's generic Eslicarbazepine Acetate Tablets in 200, 400, 600, and 800 mg dosage forms, for which Lupin submitted ANDA No. 211246 to the FDA (Compl. ¶12, ¶57).
Functionality and Market Context
- The product is a generic version of Plaintiffs' APTIOM® tablets and is intended for the treatment of partial-onset seizures in patients (Compl. ¶13, ¶38).
- As this is a Hatch-Waxman action filed pre-launch, the infringement analysis centers on the future, intended use of the product. The complaint alleges that Lupin's proposed package insert will instruct physicians and patients to administer the drug in a manner that infringes the patents-in-suit, specifically by directing a once-daily dosing regimen (Compl. ¶¶49, 69, 102, 135).
- The complaint alleges that Lupin's product is "pharmaceutically and therapeutically equivalent" to APTIOM® tablets (Compl. ¶64, ¶97, ¶130).
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
The infringement allegations are based on 35 U.S.C. § 271(e)(2), which defines the submission of an ANDA seeking approval to market a generic drug before patent expiration as a technical act of infringement. The substantive dispute concerns whether the use described in the proposed labeling for Lupin's generic product will fall within the scope of the patent claims.
U.S. Patent No. 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 | Lupin's ANDA seeks approval for its generic product for the treatment of patients with partial-onset seizures. | ¶13 | col. 16:8-12 |
| comprising administering once-daily about 1200 mg of eslicarbazepine acetate to the patient | The prescribing information for APTIOM® allegedly instructs physicians to administer a dosage of about 1200 mg once-daily for this treatment, and Lupin's proposed label will allegedly instruct the same infringing use. | ¶42-44 | col. 16:21-23 |
| wherein the patient is a human | The ANDA filing is for approval to market a prescription drug for human use. | ¶12 | col. 16:11-12 |
- Identified Points of Contention:
- Scope Questions: A central question may be the interpretation of "about 1200 mg." The dispute could focus on what range of dosages this term encompasses and whether the specific dosing instructions in Lupin's proposed label fall within that range, especially since the accused tablets come in 200, 400, 600, and 800 mg strengths (Compl. ¶57).
- Technical Questions: While not detailed in the complaint, a key technical question underlying the case will be whether the clinical data supports the patent's assertion of unexpected efficacy for once-daily dosing. The patent's validity, a likely defense, may depend on evidence demonstrating that the claimed once-daily method is non-obvious over prior art knowledge of twice-daily regimens.
U.S. Patent No. 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 | Lupin's ANDA seeks approval for its generic product for the treatment of patients with partial-onset seizures. | ¶13 | col. 15:11-13 |
| comprising administering once-daily from about 800 mg to about 1800 mg of eslicarbazepine acetate to the patient | The complaint alleges that the instructions for use of APTIOM® tablets, which Lupin's product will allegedly mirror, direct once-daily administration for treating partial-onset seizures at dosages that fall within this claimed range. | ¶48-50 | col. 16:40-42 |
| wherein the patient is a human | The ANDA filing is for approval to market a prescription drug for human use. | ¶12 | col. 15:12-13 |
- Identified Points of Contention:
- Scope Questions: Similar to the ’287 Patent, the dispute may involve whether Lupin’s proposed label instructs or encourages administration of a total daily dose that falls within the claimed "from about 800 mg to about 1800 mg" range.
- Technical Questions: The complaint's theory rests on the allegation that Lupin's label will track the brand-name APTIOM® label (Compl. ¶¶49, 102). A point of contention could arise if Lupin's proposed label provides dosing instructions that differ materially from the APTIOM® label in a way that avoids the claimed dosage ranges.
V. Key Claim Terms for Construction
- The Term: "about 1200 mg" (from claim 1 of the ’287 Patent)
- Context and Importance: The scope of this term is critical to the infringement analysis for the ’287 patent. The outcome may depend on whether the dosing regimens instructed in Lupin's proposed label, which could involve combinations of 200, 400, 600, and 800 mg tablets, are construed as being "about 1200 mg." Practitioners may focus on this term as it directly maps the claim to the accused conduct.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes a clinical study where 1200 mg once-daily was the highest dose tested and showed the greatest reduction in seizures, suggesting "about 1200 mg" could encompass a therapeutically similar range around that value (’287 Patent, col. 16:55-63; FIG. 1).
- Evidence for a Narrower Interpretation: The claims of related patents, such as claim 1 of the ’354 patent which recites a broad range ("from about 800 mg to about 1800 mg"), could be used to argue that "about 1200 mg" was intended to be a narrower, more specific limitation. The patentee’s choice to use a point value rather than a range in this claim may suggest a more limited scope.
VI. Other Allegations
- Indirect Infringement: The complaint's primary theory is induced infringement under 35 U.S.C. § 271(b). It alleges that Lupin knows of the patents-in-suit and, by seeking approval for its generic product with a proposed package insert that instructs once-daily administration, intends for physicians to prescribe and patients to use the product in a manner that directly infringes the method claims (Compl. ¶¶67-70, 100-103, 133-136).
- Willful Infringement: The complaint does not contain an explicit count for willful infringement. However, it repeatedly alleges that Lupin has knowledge of the patents-in-suit and of Plaintiffs' rights, which could form the basis for a later claim for enhanced damages under 35 U.S.C. § 283 (Compl. ¶68, ¶70, ¶101, ¶103, ¶134, ¶136).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of infringement under the Hatch-Waxman Act: will the final, FDA-approved label for Lupin’s generic product contain instructions that direct or encourage physicians and patients to administer the drug in a manner that satisfies all limitations of the asserted method claims, particularly the "once-daily" and specific dosage limitations?
- A central question for the litigation will likely be one of patent validity: are the claims covering once-daily administration non-obvious in light of prior art knowledge regarding related compounds and different dosing frequencies? The case may turn on whether Plaintiffs can defend the patentability of their discovery that once-daily dosing is unexpectedly more effective than twice-daily administration.