DCT

2:10-cv-00937

Graceway Pharma LLC v. Perrigo Co

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:10-cv-00937, D.N.J., 02/23/2010
  • Venue Allegations: Venue is alleged to be proper in the District of New Jersey based on the defendants' presence and their systematic and continuous business contacts within the state.
  • Core Dispute: Plaintiffs allege that Defendants' submission of Abbreviated New Drug Applications (ANDAs) to the FDA, seeking to market generic versions of Plaintiffs' Aldara® cream, constitutes an act of patent infringement.
  • Technical Context: The technology concerns pharmaceutical cream formulations for the drug imiquimod, an immune response modifier, where stability is improved by using a highly purified grade of oleic acid as a vehicle component.
  • Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Paragraph IV notice letters sent by Defendants Perrigo and Nycomed. These letters certified that the patent-in-suit is invalid, unenforceable, or will not be infringed by the manufacture and sale of their proposed generic products. The litigation follows the expiration of the original patent covering the imiquimod compound, positioning this formulation patent as the remaining barrier to generic entry.

Case Timeline

Date Event
1997-02-27 FDA approves Aldara® (NDA 20-723)
2004-12-17 ’672 Patent Priority Date
2007-01-10 Nycomed sends Paragraph IV Notice Letter to Graceway
2007-06-28 Perrigo Israel sends Paragraph IV Notice Letter to Graceway
2009-08-25 U.S. Patent No. 4,689,338 covering imiquimod expires
2010-02-02 ’672 Patent Issued
2010-02-23 Complaint Filed
2010-02-25 Pediatric exclusivity period for U.S. Patent No. 4,689,338 expires

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

U.S. Patent No. 7,655,672 - "Immune Response Modifier Formulations Containing Oleic Acid and Methods"

  • Issued: February 2, 2010.

The Invention Explained

  • Problem Addressed: The patent addresses the problem of chemical instability in pharmaceutical formulations that use oleic acid to solubilize an immune response modifier (IRM) compound like imiquimod. This instability, which can reduce product shelf life, was found to persist even with the addition of standard antioxidants (’672 Patent, col. 2:1-5).
  • The Patented Solution: The invention is based on the discovery that formulation stability can be significantly improved by using an oleic acid component that has "reduced amounts of polar impurities, such as peroxides, aldehydes, alcohols, and ketones" (’672 Patent, col. 2:5-9). The patent hypothesizes that these impurities in conventional oleic acid react with the IRM compound, causing it to degrade, and that using a purer form of oleic acid mitigates this issue (’672 Patent, col. 2:20-23).
  • Technical Importance: This solution provides a method for creating a stable, and therefore commercially viable, topical cream formulation for an established active pharmaceutical ingredient, overcoming a key hurdle in product development and manufacturing (’672 Patent, col. 2:9-14).

Key Claims at a Glance

  • The complaint alleges infringement of "one or more claims" of the ’672 Patent without specifying them (Compl. ¶ 41). Independent Claim 1 is representative of the core invention.
  • Independent Claim 1, Essential Elements:
    • A pharmaceutical cream for topical delivery of imiquimod.
    • Comprising a therapeutically effective amount of imiquimod.
    • Comprising a pharmaceutically acceptable vehicle that includes an oleic acid component.
    • The oleic acid component contains at least about 80% oleic acid by weight.
    • The oleic acid component has a peroxide value of less than about 5 and contains less than about 1% by weight of polar impurities.
    • The final cream formulation contains no more than about 0.03% wt./wt. of imiquimod-related impurities after 15 days of storage at ambient conditions.

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are the generic imiquimod topical creams described in ANDA No. 78-837, filed by Defendant Perrigo Israel ("Perrigo Proposed ANDA Product"), and ANDA No. 78-548, filed by Defendant Nycomed ("Nycomed Proposed ANDA Product") (Compl. ¶¶ 23, 49).

Functionality and Market Context

  • Both products are alleged to be 5% imiquimod creams formulated to be bioequivalent to Plaintiffs' commercial product, Aldara® (Compl. ¶¶ 23, 39, 49, 61). The complaint alleges the Perrigo product is formulated with 7.4% oleic acid by weight, and the Nycomed product with 25% oleic acid by weight (Compl. ¶¶ 39, 61). Crucially, the complaint alleges both Defendants will use an oleic acid component that "conforms to at least certain of the monograph compliance stipulations for super refined oleic acid NF," which Plaintiffs connect to the purity requirements of the asserted patent (Compl. ¶¶ 40, 62).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

  • Claim Chart Summary: The complaint does not include a claim chart, but the narrative allegations for both accused products map to the elements of Claim 1 of the ’672 Patent.

’672 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A pharmaceutical cream for topical application...for topical delivery of...imiquimod...comprising: a therapeutically effective amount of imiquimod; The Perrigo and Nycomed Proposed ANDA Products are topical creams formulated with 5% imiquimod. ¶¶ 39, 61 col. 11:55-56
and a pharmaceutically acceptable vehicle including an oleic acid component, The Perrigo and Nycomed products are formulated with a vehicle that includes an oleic acid component. ¶¶ 37, 59 col. 2:26-28
wherein the oleic acid component...contains at least about 80% oleic acid by weight as a fatty acid, The complaint alleges Defendants use "super refined oleic acid NF," which Plaintiffs assert meets the claimed purity level. ¶¶ 40, 62 col. 10:20-22
wherein the oleic acid component...has a peroxide value of less than about 5...and contains less than about 1% by weight polar impurities, The complaint alleges Defendants' use of "super refined oleic acid NF" will result in a formulation that meets these limitations. ¶¶ 40, 62 col. 10:23-30
and wherein said pharmaceutical cream contains imiquimod-related impurities in an amount of no more than about 0.03% wt./wt. after storage... The complaint does not provide specific test data, but alleges that a product formulated as described in the ANDAs will infringe one or more claims, implying it will meet this stability profile. ¶ 41, 63 col. 16:55-59

Identified Points of Contention

  • Technical Question: The complaint asserts that using "super refined oleic acid NF" will result in a product meeting the specific quantitative limitations of Claim 1 regarding both oleic acid purity and, critically, the final formulation's stability (i.e., the level of "imiquimod-related impurities" after storage). A primary question for the court will be what evidence Plaintiffs can produce to prove that the products as described in the ANDAs will necessarily meet these stability limitations upon manufacture.
  • Scope Questions: The interpretation of the term "about" (e.g., "about 80% oleic acid," "about 5" peroxide value) may become a point of contention, as the parties may dispute the permissible range of deviation from the recited numerical values.

V. Key Claim Terms for Construction

"oleic acid component"

  • Context and Importance: This term appears in every independent claim and is central to the invention. The infringement analysis depends on whether the oleic acid used by the Defendants, as specified in their ANDAs, falls within the scope of this term, particularly with respect to its purity and composition. Practitioners may focus on this term because its definition links the accused raw material to the patent's inventive concept.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification broadly describes the component as a "preformulation source or composition of matter containing oleic acid," which "may include other fatty acids in addition to oleic acid" (’672 Patent, col. 7:8-14). This language could support a construction that is not limited to just oleic acid itself.
    • Evidence for a Narrower Interpretation: Claim 1 requires the "oleic acid component" to contain "at least about 80% oleic acid by weight" and have specific low levels of impurities. The specification repeatedly distinguishes the invention from "compendial grade oleic acid" and links the inventive concept to "SUPER REFINED Oleic Acid NF," a specific commercial product (’672 Patent, col. 8:60-62; col. 10:29-31). This may support a narrower construction tied to these specific, high-purity characteristics.

"imiquimod-related impurities"

  • Context and Importance: The final limitation of Claim 1 defines the stability of the entire cream by reference to the maximum allowable amount of these impurities after storage. Proving infringement of this limitation requires a clear definition of what constitutes an "imiquimod-related impurity" and how it is measured.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The term itself is general and could be construed to encompass any substance resulting from the degradation of imiquimod within the formulation, regardless of the cause.
    • Evidence for a Narrower Interpretation: The patent hypothesizes that degradation is caused by polar impurities in the oleic acid reacting with the imiquimod (’672 Patent, col. 2:20-23). This could support a narrower construction limiting the term to only those specific degradation products that result from this particular reaction pathway, as opposed to degradation from other causes like light or heat.

VI. Other Allegations

Statutory Infringement

  • The complaint alleges infringement under 35 U.S.C. § 271(e)(2), which makes the submission of an ANDA seeking approval to market a patented drug a statutory act of infringement. This allows the patent holder to sue before any commercial sales of the generic product occur (Compl. ¶¶ 24, 50).

Willful Infringement

  • The complaint does not contain an explicit count for willful infringement. However, it does allege that Defendants had knowledge of the patent (or the application that led to it) via Paragraph IV notice letters dated June 28, 2007 (Perrigo) and January 10, 2007 (Nycomed) (Compl. ¶¶ 25, 51). The prayer for relief requests attorneys' fees under 35 U.S.C. § 285, which are available in "exceptional cases," a standard that may be met by a finding of willfulness or other litigation misconduct (Compl. p. 13).

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

  • A central issue will be one of evidentiary proof: Can Plaintiffs demonstrate that the generic products, as defined in the Defendants' confidential ANDA submissions, will necessarily meet the specific, quantitative purity and stability limitations recited in the asserted claims? This question is particularly acute for the claim limitation governing the level of "imiquimod-related impurities" after a defined storage period.
  • The case may also turn on a fundamental question of patentability and scope: Does claiming a pharmaceutical formulation based on the use of a known, higher-purity grade of an excipient (oleic acid) to achieve an expected result (improved stability) represent a non-obvious invention over the prior art? The court’s view on this issue will likely frame the entire dispute over infringement and validity.