DCT

1:15-cv-07121

Janssen Pharmaceutica NV v. Apotex Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:15-cv-07121, S.D.N.Y., 09/10/2015
  • Venue Allegations: Venue is alleged to be proper based on Apotex having consented to personal jurisdiction for this matter, its general business activities in the district, and its history of filing lawsuits in the Southern District of New York.
  • Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market a generic version of the SPORANOX® oral solution, constitutes an act of infringement of a patent covering formulations for poorly water-soluble drugs.
  • Technical Context: The technology concerns pharmaceutical formulation science, specifically methods for increasing the aqueous solubility and stability of drugs using chemically modified cyclodextrins.
  • Key Procedural History: This lawsuit was filed under the Hatch-Waxman Act following Defendant's submission of ANDA No. 208481 with a Paragraph IV certification, asserting the patent-in-suit is invalid, unenforceable, or not infringed. The patent-in-suit, U.S. Patent No. 6,407,079, survived an Ex Parte Reexamination, with a certificate issued on October 16, 2014, confirming the patentability of numerous claims.

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 Issue Date
2015-07-28 Date of Apotex's Paragraph IV Notice Letter
2015-09-10 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

The Invention Explained

  • Problem Addressed: The patent addresses the significant challenge that many drugs are only poorly or sparingly soluble in water, which complicates the creation of effective and stable liquid application forms, such as injection solutions ('079 Patent, col. 1:13-17). Conventional methods, including using alternative solvents or forming salts, often result in decreased efficacy, impaired chemical stability, or undesirable side effects ('079 Patent, col. 1:18-36). While a complexing agent known as β-cyclodextrin can improve solubility, its own poor water solubility (1.8 g/100 ml) and toxicity limit its therapeutic usefulness ('079 Patent, col. 1:48-53; col. 2:1-2).
  • The Patented Solution: The invention claims to solve this problem by using specific, partially etherified β-cyclodextrin derivatives to form "inclusion compounds" with poorly soluble drugs ('079 Patent, Abstract). These modified cyclodextrins—such as hydroxyethyl or hydroxypropyl β-cyclodextrin—are themselves significantly more water-soluble and less toxic than the unmodified β-cyclodextrin, allowing them to effectively solubilize the target drug in an aqueous solution without the same drawbacks ('079 Patent, col. 2:7-14, 23-26).
  • Technical Importance: This technology provided a viable pathway for formulating drugs that were previously difficult to administer in a liquid form, enabling the development of stable aqueous solutions for oral, parenteral, or topical use ('079 Patent, col. 3:56-65).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" without specifying them (Compl. ¶25). Independent claim 1 is representative of the core invention.
  • Essential elements of independent claim 1 include:
    • 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: (B-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.
  • The complaint does not explicitly reserve the right to assert dependent claims, but the general allegation for "one or more claims" preserves this option.

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Apotex's proposed generic version of SPORANOX® (itraconazole) oral solution, as described in its Abbreviated New Drug Application (ANDA) No. 208481 submitted to the FDA (Compl. ¶1, 19).

Functionality and Market Context

The complaint alleges that Janssen's own SPORANOX® oral solution is covered by the claims of the '079 Patent and is listed as such in the FDA's Orange Book (Compl. ¶17-18). The accused product is a generic version of this branded drug, meaning it is intended to have the same active ingredient, dosage form, and route of administration (Compl. ¶19). The infringement action was triggered by Apotex's filing of the ANDA, which is a statutory act of infringement under 35 U.S.C. § 271(e)(2) and signals a clear intent to enter the market upon regulatory approval (Compl. ¶19, 24).

IV. Analysis of Infringement Allegations

The complaint alleges that Apotex's proposed generic product is "covered by one or more claims of the '079 Patent" but does not provide a detailed, element-by-element infringement analysis (Compl. ¶25). The infringement theory is predicated on the allegation that the generic product is a copy of Janssen's SPORANOX® oral solution, which is itself asserted to be covered by the '079 Patent (Compl. ¶17, 19). The following chart summarizes the likely infringement positions for representative Claim 1 based on this theory.

No probative visual evidence provided in complaint.

'079 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
Pharmaceutical composition comprising an inclusion compound of (i) a drug...which is instable or only sparingly soluble in water with (ii) a partially etherified β-cyclodextrin... Apotex's ANDA product is alleged to be a generic version of SPORANOX® (itraconazole) oral solution, which contains the poorly soluble drug itraconazole formulated with a cyclodextrin derivative to form an inclusion compound. ¶19, 25 col. 3:15-24; col. 6:8
wherein the residues R are hydroxyalkyl groups and part of said residues R may optionally be alkyl groups, The formulation in Apotex's ANDA product is alleged to use a β-cyclodextrin ether with hydroxyalkyl groups, consistent with the reference drug's formulation and the patent's teachings. ¶25 col. 2:23-26
the β-cyclodextrin ether having a water solubility of greater than 1.8 g in 100 ml water, The specific β-cyclodextrin derivative used in Apotex's ANDA product is alleged to have the claimed high water solubility, which is necessary for creating the oral solution. ¶25 col. 2:7-14
wherein said composition has considerably increased water solubility and stability relative to said drugs, with very low toxicity. The final composition in Apotex's ANDA is alleged to achieve increased solubility and stability for itraconazole, which is the purpose of the formulation, and to be safe for oral administration. ¶25 col. 4:40-46; col. 6:35-42

Identified Points of Contention

  • Scope Questions: A central question will be whether the specific cyclodextrin derivative and its properties, as detailed in Apotex's confidential ANDA, fall within the scope of the term "partially etherified β-cyclodextrin" as defined by the claims. The analysis will depend on the precise chemical structure, degree of substitution, and resulting solubility of the excipient Apotex intends to use.
  • Technical Questions: The primary technical dispute will likely revolve around the comparison of Apotex's exact formulation to the claim limitations. Janssen will need to prove, through discovery of the ANDA's contents, that Apotex's product literally contains each element of an asserted claim. Apotex may argue that its formulation achieves solubility through a mechanism or with a compound that is technically distinct from what is claimed.

V. Key Claim Terms for Construction

  • The Term: "partially etherified β-cyclodextrin"
  • Context and Importance: This term is the heart of the invention, distinguishing the claimed technology from both unmodified β-cyclodextrin and certain prior art derivatives. The case's outcome may depend on whether Apotex's chosen solubilizing agent is construed as falling within this definition. Practitioners may focus on this term because Apotex could design its formulation to use a derivative that it argues is technically outside this scope.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification provides a list of suitable groups, stating the residues R can be "hydroxyethyl, hydroxypropyl or dihydroxypropyl groups" and may also include "methyl or ethyl groups" ('079 Patent, col. 2:23-28). This suggests the term covers a class of compounds rather than a single species.
    • Evidence for a Narrower Interpretation: The patent contrasts the invention with prior art dimethyl-β-cyclodextrin, which it criticizes for toxicity ('079 Patent, col. 2:62-64). A party could argue the term should be construed to require the "very low toxicity" recited in claim 1, potentially narrowing the scope to exclude any derivative that does not meet a certain safety profile. The specific molar substitution ranges provided (e.g., "between 0.05 and 10") could also be used to argue for defined boundaries ('079 Patent, col. 2:49-50).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Apotex's future commercial activities would induce and contribute to infringement by third parties (e.g., patients and doctors) (Compl. ¶26, 35). The basis for inducement would likely be the product's FDA-approved label, which would instruct users to administer the allegedly infringing composition.
  • Willful Infringement: While the complaint does not use the word "willful," it alleges the case is "exceptional" under 35 U.S.C. § 285 and that Apotex was aware of the '079 Patent but had "no reasonable basis for believing" its product would not infringe (Compl. ¶28, 29). This allegation is based on Apotex's Paragraph IV certification and its notice letter to Janssen, which establish pre-suit knowledge of the patent (Compl. ¶20, 21).

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

  • A core issue will be one of compositional fact: does the precise chemical formulation detailed in Apotex’s confidential ANDA—specifically the identity of its cyclodextrin derivative, its degree of molar substitution, and the resulting product's properties—fall within the literal boundaries of the asserted claims of the '079 patent?
  • A key legal question will be one of claim scope: how will the court construe the term "partially etherified β-cyclodextrin"? The resolution of the infringement dispute will hinge on whether this term is interpreted broadly to cover a class of solubilizing agents or more narrowly, limited by the patent’s specific examples and its stated goal of achieving "very low toxicity."