Cephalon Inc v. Sandoz Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Cephalon, Inc. (Delaware) and Cephalon France (French société par actions simplifiée)
  • Defendant: Sandoz Inc. (Colorado)
  • Plaintiff’s Counsel: Wheeler Trigg O'Donnell LLP; Finnegan, Henderson, Farabow, Garrett & Dunner, L.L.P.
• Case Identification: 1:10-cv-00175, D. Colo., 01/26/2010
• Venue Allegations: Venue is asserted based on Defendant Sandoz’s business activities within the District of Colorado, including alleged "substantial, continuous, and systematic manufacture, distribution, marketing, and/or sales of generic pharmaceutical products to residents of this judicial district."
• Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) for generic armodafinil constitutes an act of infringement of three patents covering pharmaceutical formulations, specific particle sizes, and crystalline forms of modafinil and its enantiomers.
• Technical Context: The technology relates to pharmaceutical compositions of armodafinil, the active R-enantiomer of modafinil, which is a wakefulness-promoting agent marketed by Cephalon as Nuvigil® for treating sleep disorders.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant Sandoz's filing of ANDA No. 200-511, which included a "Paragraph IV Certification" alleging that Plaintiff's patents-in-suit are invalid or would not be infringed by Sandoz's proposed generic product. Sandoz provided notice of its ANDA filing to Cephalon in a letter dated December 15, 2009.

Case Timeline

Date	Event
1994-10-06	’516 Patent Priority Date (Original Application Filing)
2001-05-25	’346 Patent Priority Date (Provisional Application Filing)
2002-01-15	’516 Patent Issue Date
2002-12-20	’570 Patent Priority Date (Foreign Application Filing)
2006-11-07	’570 Patent Issue Date
2007-11-20	’346 Patent Issue Date
2009-12-15	Sandoz sends ANDA Notice Letter to Cephalon
2010-01-26	Complaint Filing Date

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 describes the need to optimize a solid dosage form of modafinil for commercial-scale manufacturing. A particular objective was to develop a formulation with desirable properties (e.g., stability, dissolution) that could be prepared without certain common excipients like magnesium silicate or talc (’346 Patent, col. 2:11-20).
• The Patented Solution: The patent discloses specific pharmaceutical compositions comprising modafinil and a precise combination of six other excipients, each within a defined weight percentage range. These excipients include diluents, disintegrants, a binder, and a lubricant, which together are designed to create a robust and reproducible tablet using a wet granulation manufacturing process (’346 Patent, col. 3:28-65; col. 5:46-6:17).
• Technical Importance: The invention provides a specific, commercially viable formulation that ensures consistent quality and manufacturing efficiency for a widely prescribed pharmaceutical product.

Key Claims at a Glance

• The complaint alleges infringement of the patent generally, with independent claim 1 being the broadest composition claim.
• The essential elements of independent claim 1 are:
  • A composition comprising modafinil (from about 30-50% by weight);
  • a lactose monohydrate (from about 25-35% by weight);
  • a microcrystalline cellulose (from about 5-15% by weight);
  • a pregelatinized starch (from about 5-15% by weight);
  • a cross-linked sodium carboxymethyl cellulose (from about 1-10% by weight);
  • a polyvinyl pyrrolidone (from about 1-10% by weight); and
  • magnesium stearate (from about 0.2-2.0% by weight).
• The complaint does not specify assertion of dependent claims but reserves the right to do so.

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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 significantly affects the drug’s potency and safety profile. It was found that different batches of the drug produced inconsistent clinical results, including unexpected adverse events at higher doses, which was traced back to variations in particle size and, consequently, bioavailability (’516 Patent, col. 5:1-24).
• The Patented Solution: The invention claims pharmaceutical compositions of modafinil defined by a specific particle size distribution. The core of the patented solution is a "substantially homogeneous mixture" of modafinil particles wherein at least 95% of the particles have a diameter of less than about 200 microns. This control over a physical characteristic of the active ingredient is intended to ensure more predictable absorption and a consistent safety profile (’516 Patent, col. 10:49-54, Claim 1).
• Technical Importance: This patent highlights a critical aspect of pharmaceutical development, where a physical property (particle size) rather than just the chemical entity itself is a key driver of a drug’s clinical performance and safety.

Key Claims at a Glance

• The complaint asserts infringement of "at least one of the claims" of the patent (Compl. ¶23). Independent claim 1 is the broadest composition claim.
• The essential elements of independent claim 1 are:
  • A pharmaceutical composition comprising a substantially homogeneous mixture of modafinil particles,
  • wherein at least about 95% of the cumulative total of modafinil particles in said composition have a diameter of less than about 200 microns (μm).
• The complaint reserves the right to assert other claims, including dependent claims (Compl. ¶23).

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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 technical challenge that active pharmaceutical ingredients can exist in different solid-state crystal structures, known as polymorphs, which can have different stabilities and dissolution rates. The patent discloses novel crystalline forms of modafinil’s enantiomers (including armodafinil) and specific laboratory processes for producing them, typically involving controlled recrystallization from selected solvents under defined temperature conditions (’570 Patent, col. 3:41-57; col. 5:1-11).

Asserted Claims

The complaint generally alleges infringement without specifying claims (Compl. ¶34, 36).

Accused Features

The complaint alleges that the submission of the ANDA for Sandoz’s generic armodafinil product is an act of infringement, implying the product either is one of the patented crystalline forms or is made by a patented process (Compl. ¶34, 37).

III. The Accused Instrumentality

Product Identification

"Sandoz's generic armodafinil products," which are the subject of Abbreviated New Drug Application ("ANDA") No. 200-511 filed with the FDA (Compl. ¶12).

Functionality and Market Context

The accused products are generic armodafinil capsules in 50 mg, 150 mg, and 250 mg dosage strengths, intended for commercial manufacture and sale in the United States upon FDA approval (Compl. ¶12). As a generic version of Cephalon's Nuvigil®, the product is designed to be a bioequivalent substitute used to improve wakefulness in patients with certain sleep disorders (Compl. ¶1, 7). The complaint characterizes Nuvigil® as a "successful" pharmaceutical product, positioning the accused generic as a direct market competitor (Compl. ¶7). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a detailed infringement analysis or claim chart. The 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 an act of infringement. The core theory is that for Sandoz's product to be approved as a generic equivalent, it must necessarily possess the characteristics claimed in the patents-in-suit.

’346 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A composition comprising modafinil... and [six specified excipients]	Sandoz's generic armodafinil product, as described in its ANDA, is alleged to contain a formulation that meets the specific compositional limitations of the claim.	¶16	col. 6:21-41
from about 30-50%... [and specific weight % ranges for each excipient]	The excipients in Sandoz's product are alleged to be present in amounts that fall within the claimed weight percentage ranges required for bioequivalence with Nuvigil®.	¶16	col. 6:21-41

’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...	Sandoz's generic armodafinil product is alleged to be composed of modafinil particles that form a "substantially homogeneous mixture."	¶21, 23	col. 10:49-54
wherein at least about 95% of the cumulative total of modafinil particles... have a diameter of less than about 200 microns (μm).	The particle size distribution of the armodafinil in Sandoz's product is alleged to meet the specific size limitations of the claim, a parameter the patent identifies as critical to achieving the correct bioavailability.	¶21, 23	col. 10:49-54

Identified Points of Contention

• Scope Questions: A primary question for the ’346 Patent is whether Sandoz’s formulation will contain all seven listed ingredients within the claimed weight percentage ranges. For the ’516 Patent, the key question is whether Sandoz's product as defined in its ANDA actually meets the "at least about 95%... less than about 200 microns" limitation.
• Technical Questions: A factual dispute will likely arise over the specific crystalline form of armodafinil used in Sandoz's product. The infringement analysis for the ’570 Patent will depend on whether discovery reveals that Sandoz uses one of the novel, patented polymorphs or a non-infringing alternative, such as the prior art Form I polymorph mentioned in the patent’s specification (’570 Patent, col. 2:42-51).

V. Key Claim Terms for Construction

The Term: "substantially homogeneous mixture" (’516 Patent, Claim 1)

• Context and Importance: This term qualifies the nature of the modafinil particles. As it is not given a precise numerical definition in the patent, its construction is critical for determining the scope of the claim. Practitioners may focus on this term because Sandoz could argue for a narrow interpretation that its product does not meet, even if the 200-micron size limitation is satisfied.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specification discusses the goal of achieving consistency and overcoming problems from earlier, variable batches, suggesting the term could be interpreted functionally to mean a mixture consistent enough to provide a predictable clinical profile (’516 Patent, col. 5:1-24).
  • Evidence for a Narrower Interpretation: The claim immediately follows this term with the specific limitation "wherein at least about 95% of the cumulative total... have a diameter of less than about 200 microns." A party could argue that this clause serves as the definition for "substantially homogeneous," limiting its meaning to that specific quantitative requirement.

The Term: "about" (’346 Patent, Claim 1; ’516 Patent, Claim 1)

• Context and Importance: The term "about" is used to qualify all numerical ranges in the asserted claims, including the weight percentages of seven different components in the ’346 Patent and the particle size threshold in the ’516 Patent. The infringement determination will depend on how much deviation from the stated numbers this term permits.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The term is used repeatedly, suggesting a general intent to allow for standard manufacturing and measurement tolerances, consistent with general principles of claim construction.
  • Evidence for a Narrower Interpretation: The ’346 Patent includes dependent claim 2, which recites a highly specific formulation with exact percentages (e.g., "modafinil is 40.0%"). A party could argue that the use of precise values in a dependent claim implies that "about" in the independent claim should not be read so broadly as to encompass significant deviations from the patent's preferred embodiments.

VI. Other Allegations

• Indirect Infringement: The complaint alleges active inducement and contributory infringement of the ’516 and ’570 patents. The factual basis alleged is that Sandoz intends for its generic product to be used by physicians and patients in an infringing manner upon FDA approval, and that the product's labeling will instruct and encourage such infringing use (Compl. ¶22, 24-27, 36-40).
• Willful Infringement: Willfulness is alleged for all three patents. The complaint bases this on Sandoz’s knowledge of the patents, which is evidenced by its submission of a Paragraph IV certification and the accompanying notice letter sent to Cephalon (Compl. ¶17, 30, 42).

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

• A core issue will be one of evidentiary proof: What are the precise technical specifications of the Sandoz product as detailed in its confidential ANDA filing? The outcome of the case will depend heavily on a direct comparison of Sandoz's formulation data—including its full excipient list with weight percentages, its particle size distribution, and its crystalline form—against the limitations of Cephalon's asserted claims.
• A second key question will be one of claim construction: How broadly will the court interpret the term "about" as applied to the seven distinct weight percentage ranges in the ’346 patent? Infringement may turn on whether Sandoz’s formulation, if not identical, is legally equivalent under a construction of this term.
• Finally, the case raises a question of polymorphic identity: Does Sandoz's manufacturing process for armodafinil result in one of the novel crystalline forms claimed in the ’570 patent, or does it produce a non-infringing polymorph, such as the well-known Form I described in the patent as prior art?