DCT
1:10-cv-00055
Cephalon Inc v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Cephalon, Inc. (Delaware) and Cephalon France (France)
- Defendant: Sandoz Inc. (Colorado)
- Plaintiff’s Counsel: Connolly, Bove, Lodge & Hutz LLP
- Case Identification: 1:10-cv-00055, D. Del., 01/22/2010
- Venue Allegations: Venue is based on Sandoz’s alleged business of making, selling, and distributing generic pharmaceutical products in the District of Delaware.
- Core Dispute: Plaintiff alleges that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiff's Nuvigil® (armodafinil) product constitutes an act of infringement of three U.S. patents covering pharmaceutical formulations, particle size characteristics, and manufacturing methods for modafinil.
- Technical Context: The technology concerns the formulation and production of armodafinil, a wakefulness-promoting agent used to treat sleep disorders such as narcolepsy and obstructive sleep apnea.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Sandoz's filing of ANDA No. 200-511 with the U.S. Food and Drug Administration (FDA). As part of its ANDA, Sandoz submitted a "Paragraph IV Certification," asserting that Cephalon's patents are invalid or will not be infringed by Sandoz's proposed generic product. Cephalon received Sandoz's notice letter regarding the ANDA filing on or about December 16, 2009.
Case Timeline
| Date | Event |
|---|---|
| 1994-10-06 | U.S. Patent No. RE37,516 Priority Date |
| 2001-05-25 | U.S. Patent No. 7,297,346 Priority Date |
| 2002-01-15 | U.S. Patent No. RE37,516 Issued |
| 2002-12-20 | U.S. Patent No. 7,132,570 Priority Date |
| 2006-11-07 | U.S. Patent No. 7,132,570 Issued |
| 2007-11-20 | U.S. Patent No. 7,297,346 Issued |
| 2009-12-15 | Sandoz sends Paragraph IV Notice Letter to Cephalon |
| 2009-12-16 | Cephalon receives Paragraph IV Notice Letter |
| 2010-01-22 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,297,346 - Pharmaceutical Formulations of Modafinil, issued November 20, 2007
The Invention Explained
- Problem Addressed: The patent background describes a need to optimize modafinil formulations for commercial-scale manufacturing. This includes minimizing the number of excipients (inactive ingredients), avoiding the use of organic solvents in the manufacturing process, and creating stable formulations without certain ingredients like magnesium silicate or talc. (’346 Patent, col. 2:11-30).
- The Patented Solution: The invention provides a specific pharmaceutical composition that combines modafinil with a select group of common excipients: lactose monohydrate, microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, polyvinyl pyrrolidone, and magnesium stearate, all within defined percentage ranges. The patent also describes a manufacturing process involving wet mixing these components with water, followed by drying and milling, which avoids organic solvents. (’346 Patent, Abstract; col. 2:36-48).
- Technical Importance: This formulation and process provides a cost-effective and reliable method for manufacturing modafinil tablets on a commercial scale with consistent, desirable properties like stability and dissolution rate. (’346 Patent, col. 2:21-25).
Key Claims at a Glance
- The complaint does not identify specific asserted claims, but Claim 1 is the broadest independent composition claim.
- Essential elements of Independent Claim 1:
- A composition comprising modafinil, from about 30-50% of the composition by weight;
- a lactose monohydrate from about 25-35% of the composition by weight;
- a microcrystalline cellulose from about 5-15% of the composition by weight;
- a pregelatinized starch from about 5-15% of the composition by weight;
- a cross-linked sodium carboxymethyl cellulose from about 1-10% of the composition by weight;
- a polyvinyl pyrrolidone from about 1-10% of the composition by weight; and
- magnesium stearate from about 0.2-2.0% of the composition by weight.
- The complaint reserves the right to assert additional claims.
U.S. Reissue Patent No. RE37,516 E - Acetamide Derivative Having Defined Particle Size, issued January 15, 2002
The Invention Explained
- Problem Addressed: The patent discloses the discovery that the particle size of modafinil is critical to the drug's potency and safety profile, implying that inconsistent particle sizes in prior art formulations could lead to unpredictable bioavailability and clinical outcomes. (’516 Patent, col. 2:11-13).
- The Patented Solution: The invention is a pharmaceutical composition comprising modafinil particles of a specific, defined size. The claims require a "substantially homogeneous mixture" of particles where at least 95% of them have a diameter of less than about 200 microns. (’516 Patent, col. 10:49-54, Claim 1). By controlling the particle size, the formulation achieves more predictable dissolution rates and, consequently, more consistent absorption and plasma concentrations in patients. (’516 Patent, col. 9:25-34).
- Technical Importance: Controlling modafinil particle size resolved a critical manufacturing and clinical issue where different production batches of the drug exhibited different safety profiles, allowing for the creation of a more consistent and reliable final product. (’516 Patent, col. 5:3-14).
Key Claims at a Glance
- The complaint does not identify specific asserted claims, but Claim 1 is a representative independent claim.
- Essential elements of Independent Claim 1:
- A pharmaceutical composition comprising a substantially homogeneous mixture of modafinil particles,
- wherein at least about 95% of the cumulative total of said particles have a diameter of less than about 200 microns.
- The complaint reserves the right to assert additional claims.
U.S. Patent No. 7,132,570 - Method for the Production of Crystalline Forms and Crystalline Forms of Optical Enantiomers of Modafinil, issued November 7, 2006
- Technology Synopsis: This patent addresses the challenge of producing specific crystalline forms (polymorphs) of modafinil's optical enantiomers. The invention describes a process where a modafinil enantiomer is dissolved in a solvent other than ethanol and then recrystallized under specific conditions to produce a desired polymorphic form. (’570 Patent, Abstract; col. 3:50-58). Different polymorphs of a drug can have different physical properties, such as stability and solubility, which can affect its performance.
- Asserted Claims: The complaint does not specify claims but alleges infringement of one or more claims (Compl. ¶36). Independent claims include process claims 1 and 10.
- Accused Features: The complaint alleges that the process Sandoz will use to manufacture its generic armodafinil products infringes the ’570 Patent. (Compl. ¶33-34).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Sandoz's generic armodafinil products that are the subject of its ANDA No. 200-511. (Compl. ¶7, ¶12).
Functionality and Market Context
- The Sandoz products are alleged to be generic copies of Cephalon's Nuvigil® tablets, a prescription medication indicated to improve wakefulness in patients with conditions such as narcolepsy, obstructive sleep apnea/hypopnea syndrome, and shift work sleep disorder. (Compl. ¶Introduction, ¶8).
- The complaint states that Sandoz is seeking FDA approval to market its products in 50 mg, 150 mg, and 250 mg dosage strengths. (Compl. ¶12).
- No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that by submitting ANDA No. 200-511, Sandoz has committed an act of infringement under 35 U.S.C. § 271(e)(2), because the product that will be approved and marketed would infringe the patents-in-suit. The following charts summarize the infringement allegations for the lead patents based on this theory.
’346 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A composition comprising modafinil, from about 30-50%...by weight; | The complaint alleges Sandoz's ANDA describes a product that is a copy of Nuvigil® and will contain armodafinil in the claimed proportion. | ¶15-16 | col. 3:60-61 |
| a lactose monohydrate from about 25-35%...by weight; | The complaint alleges Sandoz's ANDA describes a product containing lactose monohydrate within the claimed range. | ¶15-16 | col. 3:61-67 |
| a microcrystalline cellulose from about 5-15%...by weight; | The complaint alleges Sandoz's ANDA describes a product containing microcrystalline cellulose within the claimed range. | ¶15-16 | col. 4:5-7 |
| a pregelatinized starch from about 5-15%...by weight; | The complaint alleges Sandoz's ANDA describes a product containing pregelatinized starch within the claimed range. | ¶15-16 | col. 4:10-12 |
| a cross-linked sodium carboxymethyl cellulose from about 1-10%...by weight; | The complaint alleges Sandoz's ANDA describes a product containing cross-linked sodium carboxymethyl cellulose within the claimed range. | ¶15-16 | col. 4:30-32 |
| a polyvinyl pyrrolidone from about 1-10%...by weight; | The complaint alleges Sandoz's ANDA describes a product containing polyvinyl pyrrolidone within the claimed range. | ¶15-16 | col. 4:46-49 |
| and magnesium stearate from about 0.2-2.0%...by weight. | The complaint alleges Sandoz's ANDA describes a product containing magnesium stearate within the claimed range. | ¶15-16 | col. 4:50-53 |
’516 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical composition comprising a substantially homogeneous mixture of modafinil particles, | The complaint alleges Sandoz's ANDA describes a generic product that, to be bioequivalent to Nuvigil®, will comprise a substantially homogeneous mixture of particles. | ¶20-21 | col. 3:29-33 |
| wherein at least about 95% of the cumulative total of said particles have a diameter of less than about 200 microns (um). | The complaint alleges that the product described in Sandoz's ANDA will necessarily have particles meeting this size limitation to ensure bioequivalence. | ¶20-21 | col. 3:23-29 |
Identified Points of Contention
- Factual Questions: For the '346 and '516 patents, a primary point of contention will be factual: do the specific formulation and active pharmaceutical ingredient (API) characteristics detailed in Sandoz’s confidential ANDA actually fall within the claimed percentage ranges and particle size limitations?
- Process Questions: For the '570 process patent, the key question is whether Sandoz's confidential manufacturing process for its armodafinil API employs the patented crystallization method. Proving infringement of a process patent based on an ANDA filing often presents a significant evidentiary challenge.
- Scope Questions: The interpretation of terms such as "about" and "substantially homogeneous" (discussed in Section V) may create disputes over the precise boundaries of the claims, especially if Sandoz has designed its product to be near, but not identical to, Cephalon's commercial embodiment.
V. Key Claim Terms for Construction
The Term: "about" (from Claim 1 of the ’346 Patent)
- Context and Importance: This term modifies every claimed percentage range in the '346 Patent's composition claim. Its construction is critical because it will determine the literal scope of the claimed formulation. Sandoz's infringement or non-infringement may depend on whether its formulation, if slightly outside the explicit numerical ranges, is still considered to be "about" that value.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent provides an explicit definition: "As used herein, 'about' refers to a range of values ±10% of a specified value." (’346 Patent, col. 2:55-58). Cephalon may argue this definition controls and gives clear, broad boundaries to the claims.
- Evidence for a Narrower Interpretation: Sandoz may argue that, despite the explicit definition, the term should be interpreted more narrowly in the context of the specific examples provided in the patent, or that functional considerations limit the degree of permissible variation.
The Term: "substantially homogeneous mixture" (from Claim 1 of the ’516 Patent)
- Context and Importance: This term defines the required consistency of the modafinil particles. Its interpretation is central to determining what particle distributions infringe. Practitioners may focus on this term because Sandoz could argue its particle mixture, while meeting the 95%-under-200-microns test, is not "homogeneous" in some other respect, thereby avoiding infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification provides a functional definition: "a 'substantially homogeneous mixture' of modafinil particles, as utilized herein, refers to a mixture of modafinil particles in which at least about 95% of the particles in that mixture are less than a defined size." (’516 Patent, col. 3:29-33). Cephalon will likely argue this sentence equates the term with meeting the 95% threshold.
- Evidence for a Narrower Interpretation: A defendant could argue that "homogeneous" implies characteristics beyond a simple size cutoff, such as a particular distribution shape (e.g., Gaussian) or a lack of significant outliers, and that the 95% figure is a necessary but not sufficient condition for the mixture to be "substantially homogeneous."
VI. Other Allegations
- Indirect Infringement: For the '516 and '570 patents, the complaint alleges induced and contributory infringement. The allegations are based on the premise that Sandoz will, upon FDA approval, sell its generic products with a product insert that instructs physicians and patients on how to use them, thereby inducing direct infringement by the end-users. (Compl. ¶22-29; ¶35-41).
- Willful Infringement: The complaint alleges that Sandoz has knowledge of the patents-in-suit and is "knowingly and willfully" infringing. (Compl. ¶17, ¶30, ¶42). This allegation is based on Sandoz's Paragraph IV certification, which serves as evidence that Sandoz was aware of the patents before the lawsuit was filed.
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue for the composition patents ('346 and '516) will be one of factual correspondence: does the product formulation detailed in Sandoz’s confidential ANDA—specifically its excipient percentages and API particle size distribution—fall within the literal scope of Cephalon’s claims, particularly after the term "about" is construed?
- The primary challenge for the '570 process patent will be one of evidentiary access and proof: can Cephalon, through discovery, obtain sufficient details about Sandoz's confidential API manufacturing process to prove that it practices the claimed crystallization method?
- A key legal question will be one of definitional scope: will the court adopt the explicit definitions for "about" and "substantially homogeneous mixture" provided in the patent specifications, or will it find that other intrinsic evidence or context warrants a narrower interpretation that could provide a path to non-infringement for Sandoz?