DCT

4:11-cv-02410

Genentech Inc v. Apotex Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 4:11-cv-02410, N.D. Cal., 05/17/2011
  • Venue Allegations: Venue is alleged based on Defendant’s threat to market and sell the accused product in California and its derivation of substantial revenue from sales of other pharmaceutical products in the district.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) for a generic version of the antiviral drug VALCYTE® constitutes an act of infringement of a patent covering a specific crystalline form of the active ingredient.
  • Technical Context: The technology concerns a prodrug of the antiviral agent ganciclovir, designed to improve oral bioavailability for treating cytomegalovirus (CMV) infections, particularly in immunocompromised patients.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 202785 with a Paragraph IV certification of non-infringement. The patent-in-suit is listed in the FDA's "Orange Book" as covering Plaintiffs' VALCYTE® product.

Case Timeline

Date Event
1994-07-28 U.S. Patent No. 6,083,953 Priority Date
2000-07-04 U.S. Patent No. 6,083,953 Issues
2011-04-06 Defendant sends ANDA Notice Letter to Plaintiffs
2011-05-17 Complaint Filed

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

U.S. Patent No. 6,083,953 - "2-(2-AMINO-1,6-DIHYDRO-6-OXO-PURIN-9-YL) METHOXY-1,3- PROPANEDIOL DERIVATIVE"

The Invention Explained

  • Problem Addressed: The patent’s background section explains that the potent antiviral drug ganciclovir has a "relatively low rate of absorption when administered orally" and is therefore most commonly administered via inconvenient intravenous infusion, which is particularly problematic for patients requiring long-term treatment. (’953 Patent, col. 2:46-59).
  • The Patented Solution: The invention is a specific prodrug of ganciclovir—the L-monovaline ester—which exhibits "improved oral absorption." (’953 Patent, Abstract; col. 2:60-64). The patent highlights that producing this compound in a stable, crystalline form is a "decisive advantage" because it allows for more efficient and reproducible pharmaceutical manufacturing compared to non-crystalline (amorphous) materials. (’953 Patent, col. 21:20-32).
  • Technical Importance: The invention provided a method for making ganciclovir orally bioavailable, transforming a treatment that required clinical oversight for IV administration into a more convenient oral medication. (’953 Patent, col. 5:46-52).

Key Claims at a Glance

  • The complaint does not specify claims, but the dispute centers on Claim 1, the only independent claim directed to the compound in crystalline form.
  • Independent Claim 1 requires:
    • The compound 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-3-hydroxy-1-propanyl-L-valinate hydrochloride
    • in crystalline form
  • The complaint does not explicitly reserve the right to assert dependent claims.

III. The Accused Instrumentality

Product Identification

  • The "Apotex Generic Product," which is a 450 mg tablet formulation of valganciclovir hydrochloride for which Apotex seeks FDA approval via ANDA No. 202785. (Compl. ¶¶9-10).

Functionality and Market Context

  • The accused product is an antiviral drug intended as a generic equivalent to Plaintiffs' VALCYTE® tablets. (Compl. ¶¶8-9).
  • Apotex asserts in its ANDA notice letter that its product will not infringe because it will comprise "amorphous," rather than crystalline, valganciclovir hydrochloride. (Compl. ¶10).
  • Plaintiffs allege that this amorphous form is unstable, "hygroscopic and prone to conversion to crystalline form during use by patients," such as upon exposure to ambient humidity. (Compl. ¶11, ¶17).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

’953 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
The compound 2-(2-amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-3-hydroxy-1-propanyl-L-valinate hydrochloride The Apotex Generic Product contains the active pharmaceutical ingredient valganciclovir hydrochloride. ¶10 col. 22:42-45
in crystalline form The complaint alleges that although the Apotex product is supplied as "amorphous," it will "comprise or convert to crystalline valganciclovir hydrochloride at least during use by patients, e.g. upon exposure to ambient atmospheric humidity during storage in pill trays." ¶11, ¶17 col. 22:45-46
  • Identified Points of Contention:
    • Technical Question: What evidence exists to support the allegation that the amorphous active ingredient in Apotex's product converts to a crystalline form under expected conditions of patient storage and use? The complaint states that Plaintiffs "believe and expect that... investigation will confirm" this conversion, indicating it is a central factual dispute. (Compl. ¶17).
    • Scope Questions: The case raises the question of whether an "act of infringement" under 35 U.S.C. § 271(e)(2) occurs when the ANDA is for a product supplied in a non-infringing (amorphous) state, based on the theory that it will later transform into an infringing (crystalline) state post-sale. This focuses the dispute on the timing and nature of the infringing act relative to the statutory framework.

V. Key Claim Terms for Construction

  • The Term: "crystalline form"
  • Context and Importance: This term is the lynchpin of the infringement dispute. Apotex’s non-infringement position is based on its product being "amorphous." (Compl. ¶10). Plaintiffs’ case depends on proving that the accused product meets the "crystalline form" limitation, even if through post-sale conversion. (Compl. ¶17). Practitioners may focus on this term because its definition will determine whether transient or partial crystallization is sufficient to meet the claim limitation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent does not provide a quantitative definition for "crystalline," such as a minimum percentage of crystallinity or specific X-ray diffraction peaks. This may support an argument that any detectable amount of the claimed crystalline structure meets the limitation.
    • Evidence for a Narrower Interpretation: The specification describes the crystalline form as a "decisive advantage" for enabling efficient and reproducible manufacturing and characterization. (’953 Patent, col. 21:20-32). It also provides detailed examples of processes to create a stable crystalline solid. (’953 Patent, Example 4, col. 24:10-13). This could support an argument that the term implies a stable, substantially pure crystalline material as manufactured, not a product that becomes partially crystalline due to environmental exposure.

VI. Other Allegations

  • Indirect Infringement: The complaint makes a conclusory allegation of induced and contributory infringement under 35 U.S.C. §§ 271(b) and (c). (Compl. ¶18, ¶21). However, it does not plead specific facts to support the requisite elements of knowledge and intent for inducement, such as referencing user manuals or marketing materials that would instruct or encourage an infringing use.
  • Willful Infringement: The complaint does not allege willful infringement.

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

The resolution of this case appears to hinge on two central questions:

  1. An evidentiary question of material transformation: As a matter of scientific fact, does the amorphous valganciclovir hydrochloride in Defendant's product convert to the claimed "crystalline form" under conditions reasonably expected during patient storage or use, and to what extent?

  2. A legal question of temporal scope: Can direct infringement under the Hatch-Waxman Act be established for a pharmaceutical product that is manufactured and sold in a non-infringing state, based on a theory that it will subsequently transform into an infringing state after leaving the manufacturer's control?