Janssen Pharmaceutica NV v. Xellia Pharma ApS

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Janssen Pharmaceutica N.V. (Belgium)
  • Defendant: Xellia Pharmaceuticals ApS (Denmark)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
• Case Identification: 1:16-cv-00554, D. Del., 06/29/2016
• Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware based on Defendant's transaction of business in the state, placement of products into the stream of commerce, and a Federal Circuit ruling holding that a generic drug company's application to the FDA for nationwide marketing purposefully avails itself of jurisdiction in Delaware.
• Core Dispute: Plaintiff alleges that Defendant’s filing of a New Drug Application to market a generic version of Voriconazole for Injection constitutes an act of infringement of a patent covering pharmaceutical compositions that use cyclodextrin derivatives to improve drug solubility.
• Technical Context: The technology involves advanced pharmaceutical formulation techniques designed to make drugs that are poorly soluble or unstable in water suitable for aqueous solutions, such as injectables.
• Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of a 505(b)(2) New Drug Application (NDA) and a Paragraph IV certification to the FDA. The certification asserted that U.S. Patent No. 6,407,079 is invalid. The patent-in-suit previously underwent ex parte reexamination, resulting in the confirmation of most original claims, the amendment of several claims, and the addition of new claims. The complaint alleges that in its Paragraph IV notice letter, the Defendant did not dispute that its proposed product would infringe numerous claims of the patent.

Case Timeline

Date	Event
1983-12-21	'079 Patent Priority Date
2002-06-18	'079 Patent Issue Date
2014-10-16	'079 Patent Ex Parte Reexamination Certificate Issued
2016-05-20	Defendant's Paragraph IV Notice Letter Sent to Plaintiff
2016-06-29	Complaint Filing Date

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

U.S. Patent No. 6,407,079 - “Pharmaceutical Compositions Containing Drugs Which Are Instable or Sparingly Soluble in Water and Methods for Their Preparation,” issued June 18, 2002

The Invention Explained

• Problem Addressed: The patent describes the longstanding challenge of formulating drugs that are "only poorly or sparingly soluble in water" into stable and effective aqueous solutions, such as for injection (ʼ079 Patent, col. 1:14-16). Existing methods, such as using co-solvents or forming salts, could impair stability or efficacy, while using unmodified β-cyclodextrin as a solubilizing agent was limited by its own poor water solubility (ʼ079 Patent, col. 1:17-37, 1:50-53).
• The Patented Solution: The invention is a pharmaceutical composition that pairs a poorly water-soluble drug with a specific type of solubilizing agent: a partially etherified β-cyclodextrin derivative. These modified cyclodextrins form "inclusion compounds" by encapsulating the drug molecule within their ring-like structure (ʼ079 Patent, Abstract). Unlike their unmodified counterparts, these derivatives (such as hydroxyalkyl ethers) are highly water-soluble, allowing the resulting drug-cyclodextrin complex to be dissolved in water at therapeutically relevant concentrations with improved stability and very low toxicity (ʼ079 Patent, col. 2:8-18, 7:45-48).
• Technical Importance: This technology provided a method to create stable, injectable formulations for a wide range of important drugs that were previously difficult to administer intravenously, thereby improving their bioavailability and clinical utility (’079 Patent, col. 1:38-44).

Key Claims at a Glance

• The complaint asserts infringement of claims 1-5, 12-16, 26-28, and 36-38 (Compl. ¶25). Independent claims 1, 12, 27, 31, and 36 are encompassed by the asserted claims.

• Independent Claim 1:

  • A pharmaceutical composition comprising an inclusion compound of:
  • (i) a drug capable of fitting into the cavity of the cyclodextrin ring system which is instable or only sparingly soluble in water
  • with (ii) a partially etherified β-cyclodextrin of the formula: (β-CD)—OR
  • wherein the residues R are hydroxyalkyl groups and part of said residues R may optionally be alkyl groups,
  • the β-cyclodextrin ether having a water solubility of greater than 1.8 g in 100 ml water,
  • wherein said composition has considerably increased water solubility and stability relative to said drugs, with very low toxicity.

• Independent Claim 12:

  • A pharmaceutical composition comprising an inclusion compound of (i) a drug and (ii) a β-cyclodextrin derivative of the formula (β-CD)—OR,
  • where R is selected from hydroxyethyl, hydroxypropyl, dihydroxypropyl, methyl, and ethyl or mixtures thereof;
  • provided that: (a) molar substitution by the hydroxyalkyl groups is 0.05 to 10;
  • (b) the degree of substitution by methyl and ethyl is 0 to 2.0;
  • (c) the molar ratio of drug to the derivative is from 1:6 to 4:1; and
  • (d) the water solubility of the derivative is greater than 1.8 g in 100 ml of water.

• The complaint also asserts multiple dependent claims which further narrow the scope of the drug type and the cyclodextrin derivative (Compl. ¶25).

III. The Accused Instrumentality

Product Identification

Defendant Xellia’s "Voriconazole for Injection (200 mg)," as described in its 505(b)(2) NDA No. 20-8562 ("Xellia's Product") (Compl. ¶1, ¶8).

Functionality and Market Context

Xellia's Product is described as a "generic injectable voriconazole product" (Compl. ¶8). Voriconazole is a triazole antifungal agent. The complaint alleges that Xellia seeks FDA approval to commercially manufacture and sell this product in the United States before the expiration of the '079 patent (Compl. ¶8). The complaint does not contain specific details about the chemical excipients in Xellia's formulation, beyond its identity as an injectable form of voriconazole. The infringement action arises from the statutory act of filing the NDA seeking approval for this product (Compl. ¶1).

IV. Analysis of Infringement Allegations

The complaint does not provide an element-by-element infringement analysis in the form of a claim chart. Instead, its infringement theory is predicated on a statement made by the Defendant. The complaint alleges that in a Paragraph IV Notice Letter dated May 20, 2016, "Xellia did not dispute infringement of claims 1-5, 12-16, 18-19, 23, 26-28, and 36-38 of the '079 patent" (Compl. ¶11, ¶26). The core of the infringement count is that by filing its NDA, Xellia has committed a statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), and that on the technical merits, infringement of the specified claims is not a contested issue between the parties at this stage (Compl. ¶24, ¶26).

No probative visual evidence provided in complaint.

Identified Points of Contention

• Validity vs. Infringement: The complaint frames the primary dispute as one of validity, not infringement. It states that Xellia's Paragraph IV certification alleged that the "'079 patent is invalid" (Compl. ¶11). The case may therefore focus more on Xellia's invalidity contentions than on technical disagreements over whether the accused product meets the claim limitations.
• Technical Questions: Should infringement become a contested issue, the analysis would focus on the specific composition of Xellia’s Product. A key question would be whether the solubilizing agent used in Xellia's voriconazole formulation is a "partially etherified β-cyclodextrin" that falls within the specific substitution ranges recited in claims like claim 12. As voriconazole is a triazole-based drug, its inclusion in the drug classes recited in dependent claims and claim 36 (a new claim from reexamination) may be a point of focus (’079 Patent, Reexam. Cert. col. 2:15-23).

V. Key Claim Terms for Construction

The Term: "partially etherified β-cyclodextrin" (Claim 1)

Context and Importance

This term is fundamental to the scope of the claims, defining the specific class of solubilizing agents covered by the patent. Its construction is critical for distinguishing the invention from prior art using unmodified or fully substituted cyclodextrins. Practitioners may focus on this term because its boundaries dictate which specific chemical derivatives infringe.

Intrinsic Evidence for Interpretation

• Evidence for a Broader Interpretation: The specification provides a non-exhaustive list of potential "hydroxyalkyl groups" and "alkyl groups," suggesting the term is meant to be encompassing (’079 Patent, col. 2:24-28, 55-60). Claim 1 itself uses the functional limitations of increased water solubility (>1.8 g/100 ml) and low toxicity, rather than strict structural limits, to define the scope.
• Evidence for a Narrower Interpretation: The specification provides preferred numerical ranges for substitution, such as a "molar substitution" of 0.05 to 10 for hydroxyalkyl groups and a "degree of substitution" of 0.05 to 2.0 for alkyl groups (’079 Patent, col. 2:48-50, 58-59). These preferred embodiments could be used to argue for a more constrained definition of what "partially" means in the context of the patent.

The Term: "a drug capable of fitting into the cavity of the cyclodextrin ring system" (Claim 1)

Context and Importance

This functional language defines the universe of active pharmaceutical ingredients (APIs) to which the invention applies. The term's meaning is central to determining whether a given drug, such as voriconazole, falls within the patent's scope.

Intrinsic Evidence for Interpretation

• Evidence for a Broader Interpretation: The patent lists numerous and diverse classes of drugs that are suitable, including steroids and derivatives of "benzimidazole, piperidine, piperazine, imidazole or triazole," suggesting the term is intended to cover a wide variety of chemical structures (’079 Patent, col. 3:19-24).
• Evidence for a Narrower Interpretation: A party could argue that "fitting into the cavity" implies a specific type of molecular geometry or binding interaction that is not explicitly defined, potentially opening the door to arguments that certain molecules do not "fit" in the required manner. However, the patent's extensive list of examples may counter such an argument.

VI. Other Allegations

• Indirect Infringement: The complaint alleges that if Xellia’s NDA is approved, it will actively induce infringement by marketing its product and that the product is especially made for an infringing use and not suitable for a substantial noninfringing use (Compl. ¶28, ¶29).
• Willful Infringement: The complaint alleges that Xellia acted with full knowledge of the '079 patent, based on its pre-suit Paragraph IV certification letter, and thus any subsequent infringement would be willful (Compl. ¶27, ¶38).

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

The complaint and the procedural posture of a Hatch-Waxman case frame the dispute around the following central issues for the court:

1. A central issue will be one of patent validity: As infringement is not disputed in pre-suit communications, the case will likely turn on whether Xellia can meet its burden of proving by clear and convincing evidence that the asserted claims of the '079 patent are invalid over the prior art.
2. A secondary but foundational issue will be one of claim scope and infringement: While not currently disputed, the question of whether Xellia’s voriconazole product and its specific cyclodextrin excipient fall squarely within the scope of the asserted claims remains a latent issue. The construction of terms defining the chemical structure of the cyclodextrin derivative and the re-examined claims specifically covering triazole-based drugs will be critical to resolving this question definitively.