DCT

1:19-cv-00741

OSI Pharma LLC v. Zydus Pharma USA Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00741, D. Del., 04/25/2019
  • Venue Allegations: Venue is alleged to be proper based on the court's personal jurisdiction over the defendant, and Plaintiffs' sale of the branded drug product, Tarceva®, within the judicial district.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug Tarceva® constitutes an act of infringement of a patent directed to a specific stable crystalline polymorph of the active ingredient, erlotinib hydrochloride.
  • Technical Context: The technology concerns pharmaceutical formulation, specifically the identification and isolation of a thermodynamically stable crystalline form (polymorph) of an active pharmaceutical ingredient to ensure product consistency and stability for oral administration in cancer therapies.
  • Key Procedural History: The complaint notes that on January 8, 2018, the Patent Trial and Appeal Board (PTAB) issued a Final Written Decision finding claims 44-46 and 53 of the patent-in-suit unpatentable. At the time of the complaint's filing, an appeal of that decision was pending before the U.S. Court of Appeals for the Federal Circuit, creating uncertainty around the enforceability of the specifically asserted claims.

Case Timeline

Date Event
1999-11-11 U.S. Patent No. 6,900,221 Priority Date
2005-05-31 U.S. Patent No. 6,900,221 Issue Date
2018-01-08 PTAB Final Written Decision finding claims 44-46 & 53 unpatentable
2018-05-04 Plaintiff OSI files appeal of PTAB decision to the Federal Circuit
2019-03-14 Defendant Zydus sends notice letter regarding ANDA filing
2019-03-15 Plaintiffs receive Defendant's notice letter
2019-04-25 Complaint Filing Date

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

U.S. Patent No. 6,900,221 - Stable polymorph on N-(3-ethynylphenyl)-6, 7-bis (2methoxyethoxy)-4-quinazolinamine hydrochloride, methods of production, and pharmaceutical uses thereof

Issued May 31, 2005

The Invention Explained

  • Problem Addressed: The patent addresses the need for a stable, solid form of the drug compound erlotinib hydrochloride suitable for oral administration, such as in tablets (’221 Patent, col. 1:49-62). The specification notes that stability is a significant concern for the hydrochloride form of the compound, as variations in its crystalline structure can affect dosage level and administration efficacy (’221 Patent, col. 8:26-29).
  • The Patented Solution: The invention is the identification and preparation of a specific, thermodynamically stable crystalline form of erlotinib hydrochloride, which the patent designates "Polymorph B" (’221 Patent, col. 8:33-35). This polymorph is characterized by a unique X-ray powder diffraction (XRPD) pattern with specific peaks, as illustrated in Figure 3 of the patent (’221 Patent, col. 2:27-36, Fig. 3). By isolating this stable form, the invention provides a more reliable and desirable active ingredient for use in solid pharmaceutical compositions.
  • Technical Importance: The patent explains that the erlotinib hydrochloride compound disclosed in prior art was actually a mixture of the less-stable Polymorph A and the stable Polymorph B, and that this mixture's "partially reduced stability" made it less preferred for tablet formulations (’221 Patent, col. 8:41-48). The isolation of the pure, stable "Polymorph B" was therefore a key step in developing a commercially viable oral drug product.

Key Claims at a Glance

  • The complaint specifically asserts method of use claims 44-46 and 53 (Compl. ¶20). These claims depend on the underlying patented composition. The foundational composition claim, from which the dispute arises, is independent claim 3:
  • Independent Claim 3:
    • A crystalline polymorph of the hydrochloride salt of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine designated the B polymorph
    • that exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2-theta at approximately 6.26, 12.48, 13.39, 16.96, 20.20, 21.10, 22.98, 24.46, 25.14 and, 26.91,
    • which is free of the A polymorph.
  • The complaint reserves the right to assert additional claims of the ’221 patent (Compl. ¶20).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is the "Zydus ANDA product," which comprises 25 mg, 100 mg, and 150 mg tablets of erlotinib hydrochloride, for which Defendant Zydus seeks FDA approval via ANDA No. 213065 (Compl. ¶1-2).

Functionality and Market Context

The complaint alleges that Zydus's product is a generic version of Plaintiffs' Tarceva® drug product (Compl. ¶2). As part of its ANDA filing, Zydus has represented to the FDA that its product has the same active ingredient, dosage form, and strength as Tarceva®, and is bioequivalent to Tarceva® (Compl. ¶14). Zydus is seeking approval for the same medical indications as Tarceva®, which is a kinase inhibitor used for treating certain types of non-small cell lung cancer and pancreatic cancer (Compl. ¶11, ¶15). The filing of the ANDA itself is the statutory act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶20).

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or detailed, element-by-element infringement analysis. The infringement allegations are based on the statutory framework of the Hatch-Waxman Act, where the filing of an ANDA seeking approval to market a generic drug before the expiration of a relevant patent is a technical act of infringement (Compl. ¶20). The central theory of infringement is that for the Zydus ANDA product to be bioequivalent to Plaintiffs' Tarceva® product, it must necessarily contain the same active ingredient, erlotinib hydrochloride, in the specific stable crystalline form—Polymorph B—that is protected by the claims of the ’221 patent. The complaint alleges that upon FDA approval, Zydus's commercial manufacture, use, and sale of the product would constitute direct and indirect infringement (Compl. ¶21-22).

No probative visual evidence provided in complaint.

V. Key Claim Terms for Construction

The Term: "free of the A polymorph"

  • Context and Importance: This limitation in claim 3 defines the required purity of the claimed Polymorph B. The construction of this term is critical for both infringement and validity. The dispute will center on whether "free of" means an absolute, 100% absence of Polymorph A, or if it permits trace amounts below a certain threshold of detection or commercial significance.
  • Intrinsic Evidence for a Broader Interpretation: The specification uses terms like "substantially homogeneous" and "substantially pure" when describing the invention, which may suggest that the claims do not require absolute purity (’221 Patent, col. 2:27, col. 2:49).
  • Intrinsic Evidence for a Narrower Interpretation: The claim explicitly uses the term "free of," rather than "substantially free of." The specification also describes compositions with specific minimum weight percentages of Polymorph B (e.g., "at least 70%"), suggesting "free of" is a distinct and higher standard than those explicitly quantified levels of purity (’221 Patent, col. 3:1-11).

The Term: "approximately"

  • Context and Importance: This term modifies the numerical values of the XRPD peaks that characterize Polymorph B in the claims. Practitioners may focus on this term because its scope will determine how closely the XRPD pattern of the Zydus product must match the patent's values to be considered infringing.
  • Intrinsic Evidence for a Broader Interpretation: The patent's use of "approximately" in the claims, while providing more precise values in specification tables (e.g., Table 3), suggests an acknowledgment of inherent experimental variability in XRPD analysis and that the claimed values are not meant to be rigid, absolute numbers (’221 Patent, col. 12:35-50).
  • Intrinsic Evidence for a Narrower Interpretation: A party could argue that "approximately" is only intended to cover minor, routine instrumental error and cannot be broadened to encompass a product with a genuinely different crystalline structure that produces consistently different, though close, peak values.

VI. Other Allegations

Indirect Infringement

The complaint alleges that Zydus's future commercial activities would constitute induced and contributory infringement (Compl. ¶21, ¶22). The factual basis for this allegation is Zydus's intent to market its ANDA product with a label that will instruct physicians and patients to administer the drug for its approved indications, which correspond to the methods of treatment recited in the asserted claims.

Willful Infringement

The complaint does not contain an explicit allegation of willful infringement or a request for enhanced damages. However, it does allege that Zydus had pre-suit knowledge of the ’221 patent via a "Tarceva Notice Letter" dated March 14, 2019 (Compl. ¶12). This allegation could potentially form the basis for a later claim of post-filing willfulness.

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

  • A primary issue in this case, from the perspective of the complaint's filing date, is one of claim enforceability: given that the PTAB had found the specifically asserted claims (44-46 and 53) unpatentable in a decision that was pending appeal, what is the valid and enforceable scope of the patent-in-suit?
  • A key evidentiary question will be one of technical identity and purity: does the erlotinib hydrochloride in Zydus's proposed generic product, as defined in its ANDA, exist as the specific "Polymorph B" characterized by the patent's XRPD peaks, and can Plaintiffs prove it is "free of the A polymorph" as required by the core composition claim?
  • The case may also turn on a question of definitional precision: how will the court construe the term "free of," and will it require absolute purity or allow for trace impurities? The answer will directly impact both the infringement and validity analyses.