DCT
2:07-cv-04937
Acorda Therap Inc v. Apotex Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Acorda Therapeutics, Inc. (Delaware)
- Defendant: Apotex Inc. (Canada) and Apotex Corp. (Delaware)
- Plaintiff’s Counsel: GIBBONS P.C.
- Case Identification: 2:07-cv-04937, D.N.J., 10/11/2007
- Venue Allegations: Venue is alleged to be proper based on Defendants’ business activities within the judicial district, previous submission to the Court's jurisdiction in other matters, and the district being a likely destination for the accused generic products.
- Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) for generic tizanidine hydrochloride capsules constitutes an act of infringement of a patent covering a method of administering the drug to reduce the side effect of somnolence.
- Technical Context: The technology relates to pharmaceutical formulations and methods of use for tizanidine, a centrally-acting muscle relaxant used to treat spasticity, with a focus on mitigating known side effects through specific administration protocols.
- Key Procedural History: This patent infringement action was initiated under the Hatch-Waxman Act, triggered by Defendants' filing of ANDA No. 78-868 with the FDA. This filing included a "Paragraph IV certification," a declaration that the patent-in-suit is invalid, unenforceable, or will not be infringed by the proposed generic product. The patent-in-suit is listed in the FDA's "Orange Book" for Plaintiff's branded product, Zanaflex Capsules™.
Case Timeline
| Date | Event |
|---|---|
| 2001-11-28 | U.S. Patent No. 6,455,557 Priority Date |
| 2002-08-29 | Acorda's NDA No. 02-1447 for tizanidine hydrochloride capsules approved |
| 2002-09-24 | U.S. Patent No. 6,455,557 Issued |
| 2007-08-28 | Apotex's Notice of Certification letter for ANDA No. 78-868 dated |
| 2007-10-11 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,455,557 - METHOD OF REDUCING SOMNOLENCE IN PATIENTS TREATED WITH TIZANIDINE
- Patent Identification: U.S. Patent No. 6,455,557, METHOD OF REDUCING SOMNOLENCE IN PATIENTS TREATED WITH TIZANIDINE, issued September 24, 2002.
The Invention Explained
- Problem Addressed: The patent describes tizanidine as an effective treatment for spasticity that is accompanied by a significant and potentially dangerous side effect: somnolence, or drowsiness (’557 Patent, col. 2:46-54). The background section notes that for conventional tablet formulations of tizanidine, administration with food increases the drug's peak plasma concentration (Cmax), which can exacerbate somnolence (’557 Patent, col. 2:30-34). This creates a clinical need for a method to administer tizanidine that minimizes this adverse effect (’557 Patent, col. 3:9-14).
- The Patented Solution: The patent discloses a method of reducing somnolence by administering tizanidine in a specific physical form—an "immediate release multiparticulate pharmaceutical composition" (e.g., beads within a capsule)—with food (’557 Patent, col. 3:24-32). The specification asserts the surprising discovery that, unlike the tablet form, administering this multiparticulate formulation with food blunts the peak plasma concentration and reduces overall somnolence compared to other administration regimens, as illustrated by pharmacokinetic data in the patent (’557 Patent, FIG. 1; col. 3:24-32).
- Technical Importance: This method offered a way to improve the safety profile and therapeutic utility of tizanidine by decoupling its administration from an increase in a significant dose-limiting side effect (’557 Patent, col. 3:9-14).
Key Claims at a Glance
- The complaint alleges infringement of "at least one claim" without specifying which ones (Compl. ¶15). Independent claim 1 is representative of the asserted technology.
- Independent Claim 1:
- A method of reducing somnolence in a patient receiving tizanidine therapy comprising administering to the patient a therapeutically effective amount of tizanidine
- in an immediate release multiparticulate pharmaceutical composition
- with food,
- wherein administration of the composition with food produces a peak plasma tizanidine concentration earlier than about 4 hours from administration.
- The complaint’s broad allegation suggests it may reserve the right to assert other claims, including dependent claims.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is Defendants' proposed generic drug product: capsules containing 2, 4, and 6 mg of tizanidine hydrochloride, for which Apotex filed ANDA No. 78-868 with the FDA (Compl. ¶¶4, 13).
Functionality and Market Context
- The filing of the ANDA is the statutory act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶15). The Apotex product is intended to be a generic version of Plaintiff's Zanaflex Capsules™ (Compl. ¶13). The complaint alleges that Apotex seeks approval for a proposed product label that is "the same, or substantially the same, as the Zanaflex Capsules™ labeling" (Compl. ¶16). This proposed label, which would instruct patients and physicians on the product's use, forms the basis for the allegations of induced infringement.
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
The complaint does not contain a claim chart. The infringement theory, typical in ANDA litigation, is that the use of Apotex's generic product as directed by its proposed label will infringe the method claims of the ’557 patent.
’557 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of reducing somnolence...comprising administering...a therapeutically effective amount of tizanidine | Apotex's product is a generic tizanidine hydrochloride formulation in therapeutically effective dosages (2, 4, and 6 mg) intended for the same medical indications. | ¶13 | col. 1:4-8 |
| in an immediate release multiparticulate pharmaceutical composition | Apotex's product is formulated as "capsules," which are intended to be generic versions of Acorda's multiparticulate Zanaflex Capsules™. | ¶13 | col. 4:22-28 |
| with food, | The proposed label for Apotex's product is alleged to be the same as the label for Zanaflex Capsules™, which would contain instructions regarding administration with food. | ¶16 | col. 4:38-44 |
| wherein administration of the composition with food produces a peak plasma tizanidine concentration earlier than about 4 hours from administration. | The ANDA filing for Apotex's generic capsules necessarily contains bioequivalence data intended to show its pharmacokinetic (PK) profile matches the reference listed drug, which itself meets this PK parameter. | ¶¶12-13 | col. 8:5-15, Table I |
- Identified Points of Contention:
- Scope Questions: A central question is whether Apotex's specific formulation, as detailed in its confidential ANDA, meets the definition of an "immediate release multiparticulate pharmaceutical composition" as that term is construed in light of the patent's specification.
- Technical Questions: A key factual dispute will concern the pharmacokinetic data submitted in Apotex's ANDA. Does that data confirm that administration of the Apotex generic capsule with food results in a peak plasma concentration (Tmax) of less than 4 hours, as required by the claim?
- Legal Questions (Inducement): The case will likely turn on whether Apotex's proposed product label "actively and knowingly" encourages or instructs physicians and patients to administer the drug with food for the purpose of reducing somnolence, thereby satisfying the legal standard for induced infringement. The precise wording of the label will be critical.
V. Key Claim Terms for Construction
The Term: "multiparticulate pharmaceutical composition"
- Context and Importance: This term defines the physical form of the drug delivery system. The patent's core inventive concept rests on the different pharmacokinetic behavior of this "multiparticulate" form compared to a conventional tablet. Practitioners may focus on this term because the infringement analysis depends on whether Apotex's generic capsule formulation falls within its scope.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a broad definition: "a plurality of discrete particles, pellets, mini-tablets and mixtures or combinations thereof" (’557 Patent, col. 4:22-24).
- Evidence for a Narrower Interpretation: The specification also describes a preferred embodiment in detail as "a population of immediate release beads having tizanidine layered over non-pareil seeds" (’557 Patent, col. 4:30-33). A party could argue that the term should be understood in the context of this more specific embodiment.
The Term: "with food"
- Context and Importance: The method is expressly limited to administration "with food." The interpretation of this term determines the circumstances under which infringement could occur.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent explicitly defines a wide window for administration: "between about 30 minutes prior to about 2 hours after eating a meal" (’557 Patent, col. 4:52-55).
- Evidence for a Narrower Interpretation: The patent also identifies a "most" preferred timing: "substantially the same time as the eating of the meal" (’557 Patent, col. 4:55-57). Additionally, "food" is defined with some specificity as "a solid food with sufficient bulk and fat content that it is not rapidly dissolved and absorbed in the stomach" (’557 Patent, col. 4:50-52).
VI. Other Allegations
- Indirect Infringement: The complaint explicitly alleges induced infringement under 35 U.S.C. § 271(b). The factual basis for this claim is that Apotex's proposed product labeling, by being the same or substantially the same as the Zanaflex Capsules™ label, will "actively and knowingly induce, encourage, aid and abet patients and doctors" to use the generic product in a manner that directly infringes the patented method (Compl. ¶¶16-17).
- Willful Infringement: The complaint does not use the term "willful," but it requests that the court declare the case "exceptional" under 35 U.S.C. § 285 and award attorneys' fees (Compl. p. 6, ¶5). The allegation that Apotex acted "knowingly" to induce infringement (Compl. ¶17), combined with the fact that Apotex was aware of the patent as evidenced by its ANDA notice letter (Compl. ¶14), could form the basis for such a finding.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of induced infringement: Does the specific language of Apotex's proposed product label go beyond merely stating the pharmacokinetic effects of food and instead actively instruct or encourage administering the generic capsules with food for the claimed purpose of reducing somnolence? The outcome may depend on whether the label creates the specific intent required for inducement.
- A key evidentiary question will be one of pharmacokinetic equivalence: Does the bioequivalence data within Apotex’s confidential ANDA filing demonstrate that its generic product, when taken with food, exhibits the specific peak plasma concentration timing (Tmax < 4 hours) mandated by claim 1? This will determine whether the use described in the label would constitute direct infringement, a prerequisite for the inducement claim.