DCT

1:18-cv-01818

Astellas Pharma Inc v. Xellia Pharma ApS

Log In
Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:18-cv-01818, D. Del., 11/19/2018
  • Venue Allegations: Venue is asserted based on Defendant Xellia Pharmaceuticals, Inc. being a Delaware corporation and both defendants allegedly conducting systematic and continuous business in the state, making Delaware a likely destination for the accused generic drug products.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of Plaintiff's antifungal drug Mycamine® constitutes an act of infringement of a patent covering a stabilized, lyophilized formulation of the drug.
  • Technical Context: The technology concerns pharmaceutical formulations designed to improve the chemical stability and shelf-life of micafungin, a complex cyclic polypeptide compound used in intravenous treatments for serious fungal infections.
  • Key Procedural History: This is a Hatch-Waxman action triggered by a Notice Letter, dated October 8, 2018, in which Defendant Xellia notified Plaintiff of its ANDA filing with a Paragraph IV certification, asserting non-infringement, unenforceability, or invalidity of the patent-in-suit. The complaint was filed within the 45-day statutory period, which typically imposes a 30-month stay on the FDA’s approval of the generic product.

Case Timeline

Date Event
1999-07-01 ’104 Patent Priority Date
2004-08-10 ’104 Patent Issue Date
2005-03-16 FDA Approval of Mycamine® (50 mg/vial)
2006-06-27 FDA Approval of Mycamine® (100 mg/vial)
2018-10-08 Defendant sends Paragraph IV Notice Letter to Plaintiff
2018-11-19 Complaint Filing Date
2021-01-08 ’104 Patent Expiration Date (as alleged in complaint)

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 6,774,104 - *Stabilized Pharmaceutical Composition in Lyophilized Form*

  • Patent Identification: U.S. Patent No. 6,774,104, "Stabilized Pharmaceutical Composition in Lyophilized Form," issued August 10, 2004.

The Invention Explained

  • Problem Addressed: The patent's background section states that the class of cyclic polypeptide compounds to which the active ingredient micafungin belongs is "generally unstable to light, humidity, acids, heat and the like" (’104 Patent, col. 2:59-62). This instability complicates the development of pharmaceutical preparations with a commercially viable shelf-life.
  • The Patented Solution: The invention addresses this stability problem by formulating the active compound with a stabilizer and then lyophilizing (freeze-drying) the mixture (’104 Patent, Abstract). The resulting "cake" or powder can be stored for long periods and then reconstituted with a liquid for injection. The patent provides data suggesting that including a stabilizer, such as lactose, significantly reduces the degradation of the active compound over time compared to a formulation without a stabilizer (’104 Patent, col. 11, Table 1).
  • Technical Importance: For complex, injectable biologic drugs, achieving a formulation that remains stable and potent through manufacturing, shipping, and storage is a critical and non-trivial technical hurdle for bringing a product to market.

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 16, as well as dependent claims 3, 8, 17, and 18 (Compl. ¶39).
  • Independent Claim 1:
    • A stabilized pharmaceutical composition in lyophilized form which comprises:
    • a cyclic polypeptide compound of the formula (I) or its pharmaceutically acceptable salt, and
    • lactose.
  • Independent Claim 16 (via claims 13 and 1):
    • A method for treating a fungal disease
    • comprising administering an effective amount of a composition comprising [the composition of claim 1] and water
    • to a subject in need thereof.

III. The Accused Instrumentality

Product Identification

The accused instrumentalities are Defendant Xellia's proposed generic drug products that are the subject of ANDA No. 211713 ("ANDA Products") (Compl. ¶31).

Functionality and Market Context

The ANDA Products are described as generic versions of Plaintiff's commercial Mycamine® product (Compl. ¶¶16, 27). They are intended to be sold as lyophilized powders for injection in 50 mg/vial and 100 mg/vial dosage forms (Compl. ¶31). The complaint alleges these products contain the active ingredient micafungin sodium and the excipient lactose, and are intended for the treatment of infectious diseases (Compl. ¶31).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

  • Claim Chart Summary: The complaint alleges that the filing of the ANDA constitutes infringement under 35 U.S.C. § 271(e)(2) because the product described therein, if commercially manufactured and sold, would infringe the ’104 patent.

’104 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A stabilized pharmaceutical composition in lyophilized form which comprises: The complaint alleges Xellia’s ANDA Products are "pharmaceutical composition[s] in an injectable dosage form," which are typically lyophilized. The asserted claims cover such stabilized, lyophilized compositions. ¶31, ¶39 col. 16:7-8
a cyclic polypeptide compound of the formula (I)... or its pharmaceutically acceptable salt, The ANDA Products are alleged to contain "micafungin sodium as active ingredient." Micafungin sodium is identified as a salt of micafungin, the compound covered by formula (I). ¶16, ¶25, ¶31 col. 16:8-10
and lactose. The ANDA Products are alleged to contain "lactose as a pharmaceutical composition." ¶16, ¶31 col. 16:11

Identified Points of Contention

  • Scope Questions: A central question may be the proper construction of the term "stabilized." The complaint alleges infringement by asserting the accused product contains the claimed ingredients, but it does not provide data or a specific theory as to how the accused product meets the "stabilized" limitation. The dispute may turn on whether "stabilized" requires a specific, quantitative level of stability improvement or is inherently met by combining micafungin and lactose as taught in the patent.
  • Technical Questions: What evidence will be presented to demonstrate that Xellia's proposed formulation is, in fact, "stabilized" as the term is construed? The infringement analysis will likely depend on a factual comparison of the stability characteristics of Xellia's ANDA product against the teachings of the ’104 patent specification.

V. Key Claim Terms for Construction

  • The Term: "stabilized"
  • Context and Importance: This term appears in the preamble of claim 1 but may be treated as a limitation because it breathes life and meaning into the claim and is relied upon in the specification to distinguish the invention over the prior art problem of instability. The entire purpose of the invention is to create a "stabilized" composition. The outcome of the case may depend on whether Xellia's product, which contains the same key ingredients, falls within the scope of this term.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The claims do not recite a specific numerical threshold for stability. A party could argue that any formulation containing lactose with micafungin is "stabilized" relative to the unstable compound alone, consistent with the patent's general teaching.
    • Evidence for a Narrower Interpretation: The specification includes examples with specific stability data, showing the formulation with lactose retaining 99.5% of the compound after nine days at 70° C., while the control without a stabilizer retained less than 75% (’104 Patent, col. 11, Table 1). A party could argue that "stabilized" should be construed to require a meaningful and significant improvement in stability, as demonstrated in the patent's own examples.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges infringement of method claim 16, which covers treating a fungal disease by administering the claimed composition (Compl. ¶¶39-40). The allegation is premised on the future use of the ANDA Products. Evidence for inducement would likely focus on Xellia's "proposed label," which allegedly will instruct physicians and other healthcare providers to reconstitute and administer the drug in an infringing manner (Compl. ¶40).
  • Willful Infringement: The complaint does not use the word "willful" but alleges the case is "exceptional" under 35 U.S.C. § 285, which provides a basis for seeking attorney fees (Compl. ¶41). The factual basis alleged is that Xellia knew of the ’104 patent at least as of its submission of the Paragraph IV certification letter (Compl. ¶17).

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

  • A core issue will be one of definitional scope: can the term "stabilized", which is presented as the key inventive concept, be construed to cover any lyophilized formulation containing micafungin and lactose, or does it require proof of a specific, heightened level of chemical stability as demonstrated in the patent’s examples?
  • A key evidentiary question for indirect infringement will be whether Xellia’s proposed drug label will direct medical professionals to reconstitute and administer the ANDA product in a manner that performs all steps of the asserted method claims, thereby inducing infringement.