DCT

2:11-cv-00807

Palmetto Pharma LLC v. AstraZeneca Pharma LP

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:11-cv-00807, D.S.C., 04/05/2011
  • Venue Allegations: Venue is asserted on the basis that the defendant has committed acts of infringement in the district and is subject to personal jurisdiction there.
  • Core Dispute: Plaintiff alleges that Defendant’s marketing and sale of the drug Crestor induces infringement of a patent claiming a method of using Hmg-CoA reductase inhibitors (statins) to increase nitric oxide production in nonhyperlipidemic patients.
  • Technical Context: The technology concerns a secondary therapeutic use for statins, a major class of cardiovascular drugs, suggesting they provide benefits beyond their primary cholesterol-lowering function.
  • Key Procedural History: The patent-in-suit, U.S. Patent No. 6,465,516, underwent an ex parte reexamination that concluded with the issuance of a Reexamination Certificate on the same day the complaint was filed. This proceeding resulted in the amendment of the asserted independent claim, narrowing its scope from treating any subject to treating only "nonhyperlipidemic" subjects. This amendment, made to secure the patent's validity, will be a central focus of the infringement analysis.

Case Timeline

Date Event
1997-04-10 '516 Patent Priority Date
2002-10-15 '516 Patent Issue Date
2011-04-05 '516 Patent Reexamination Certificate Issue Date
2011-04-05 Complaint Filing Date

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

  • U.S. Patent No. 6,465,516 (as reexamined), Method of Stimulating Nitric Oxide Synthase, issued October 15, 2002

The Invention Explained

  • Problem Addressed: The patent’s background discusses the treatment of cardiovascular disease. While Hmg-CoA reductase inhibitors (statins) were well-known for reducing cholesterol, the patent asserts that prior to the invention, there was "no known research indicating Hmg-CoA reductase inhibitors were capable of functioning as agonist of CNOS" (constitutive nitric oxide synthase) to produce vasodilatory effects. (’516 Patent, col. 2:47-51).
  • The Patented Solution: The invention is a method of using a statin to treat patients who would benefit from increased nitric oxide (NO) production, independent of the drug's cholesterol-lowering mechanism. (’516 Patent, Abstract). The patent describes this as a "dual applicability" for statins, acting as both cholesterol inhibitors and stimulators of nitric oxide synthase. (’516 Patent, col. 4:46-50).
  • Technical Importance: The invention proposed a novel mechanism of action for one of the world's most prescribed drug classes, suggesting a therapeutic benefit for patients who were not candidates for statin therapy based on cholesterol levels alone. (’516 Patent, col. 10:20-25).

Key Claims at a Glance

  • The complaint asserts reexamined independent claim 1. (Compl. ¶10).
  • The essential elements of reexamined claim 1 are:
    • A method for treating a nonhyperlipidemic subject
    • who would benefit from increased Nitric Oxide production in a tissue
    • comprising: administering to the nonhyperlipidemic subject in need of such treatment
    • a Hmg-CoA reductase inhibitor
    • in an amount effective to increase Nitric Oxide production in said tissue of the subject.
  • The complaint notes the infringement of dependent reexamined claims 4 and 7, as well as newly added dependent claims 15-20, which specify treatments to reduce the risk of stroke, angina, and reperfusion injury. (Compl. ¶10; ’516 C1 Certificate, col. 2:15-25).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the prescription drug Crestor (rosuvastatin calcium). (Compl. ¶8).

Functionality and Market Context

  • Crestor is an Hmg-CoA reductase inhibitor. (Compl. ¶8). The complaint alleges that AstraZeneca promotes and encourages the use of Crestor for a specific patient population: "individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease based on age ≥ 50 years old in men and ≥ 60 years old in women, hsCRP > 2mg/L, and the presence of at least one additional cardiovascular disease risk factor..." (Compl. ¶9). The complaint alleges this use is indicated to reduce the risk of stroke, myocardial infarction, and arterial revascularization procedures, which are outcomes the patent suggests are treatable via increased NO production. (Compl. ¶9).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'516 Patent Infringement Allegations

Claim Element (from Reexamined Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating a nonhyperlipidemic subject... AstraZeneca's package insert for Crestor allegedly instructs administration to "individuals without clinically evident coronary heart disease but with an increased risk of cardiovascular disease..." a population Plaintiff will need to prove is "nonhyperlipidemic." ¶9 col. 10:27-28
...who would benefit from increased Nitric Oxide production in a tissue... The instructions for Crestor are for reducing the risk of stroke and myocardial infarction, conditions which the patent asserts are benefited by increased NO production. ¶9 col. 3:36-49
...comprising: administering to the nonhyperlipidemic subject in need of such treatment, a Hmg-CoA reductase inhibitor... AstraZeneca makes and sells Crestor (rosuvastatin calcium), an Hmg-CoA reductase inhibitor, and its package insert allegedly instructs its administration. ¶¶8-9 col. 10:22-23
...in an amount effective to increase Nitric Oxide production in said tissue of the subject. The complaint alleges that following the instructions for Crestor constitutes infringement, implicitly asserting that the prescribed dosage is effective to increase NO production, a theory supported by experimental data in the patent. ¶10 col. 4:45-53
  • Identified Points of Contention:
    • Scope Questions: The primary dispute will concern the scope of "nonhyperlipidemic subject." Does the patient population described on the Crestor label—defined by age, risk factors, and elevated hsCRP, but not necessarily by cholesterol levels—fall within the claim term that was added during reexamination to narrow the patent?
    • Technical Questions: What evidence demonstrates that the prescribed dose of Crestor performs the function of increasing Nitric Oxide production, as required by the claim, and that AstraZeneca's instructions for use induce physicians to practice the patented method for this purpose?

V. Key Claim Terms for Construction

  • The Term: "nonhyperlipidemic subject"
  • Context and Importance: This term is the lynchpin of the case. It was not in the original claim but was added during reexamination, presumably to overcome prior art and save the patent from invalidity. Its definition will determine whether the patient population for which Crestor is marketed infringes the claim. Practitioners may focus on this term because the infringement analysis for this induced infringement claim depends entirely on whether the patient profile in Crestor's label matches this limiting term.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification does not provide an explicit numerical definition. A party could argue it means any subject who does not have a formal diagnosis of hyperlipidemia or whose cholesterol levels are not the primary basis for treatment. The original patent included dependent claim 2, "The method of claim 1 wherein the subject is nonhyperlipidemic," without further definition, suggesting the patentee viewed it as a distinct and understood patient class. (’516 Patent, col. 10:27-28).
    • Evidence for a Narrower Interpretation: An opposing party could argue the term requires a specific, low cholesterol level (e.g., low LDL-C), pointing to the specification’s goal of distinguishing its method from conventional cholesterol-lowering treatments. The lack of a precise definition in the specification suggests the term's meaning may be confined to the context of treating conditions where cholesterol is not a factor.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement under 35 U.S.C. § 271(b), asserting that AstraZeneca’s package insert "promotes and encourages the use of Crestor" in a manner that directly infringes the method claims. (Compl. ¶¶ 9, 12). The complaint also makes a parallel allegation of contributory infringement. (Compl. ¶13).
  • Willful Infringement: The complaint alleges that AstraZeneca possessed "actual knowledge of the ‘516 patent" and was aware that the instructed use of Crestor infringes the reexamined claims. (Compl. ¶10). This allegation, coupled with the request for enhanced damages, forms the basis for a willfulness claim. (Compl., Prayer for Relief ¶2).

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

  • A core issue will be one of definitional scope: can the term "nonhyperlipidemic subject," which was added during reexamination to limit the patent, be construed to cover the patient population described in the Crestor label—a group defined by cardiovascular risk factors and inflammatory markers rather than cholesterol levels?
  • A second key question will be one of intent and causation: can Palmetto prove not only that the instructed use of Crestor results in increased nitric oxide production, but also that AstraZeneca’s marketing and labeling demonstrate a specific intent to encourage physicians and patients to perform the patented method, thereby satisfying the requirements for induced infringement?