DCT
2:13-cv-02078
MUSC Foundation for Research Development v. AstraZeneca Pharma LP
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: MUSC Foundation for Research Development and Charleston Medical Therapeutics, Inc. (South Carolina)
- Defendant: AstraZeneca Pharmaceuticals LP (Delaware)
- Plaintiff’s Counsel: Motley Rice LLC; McKool Smith, P.C.
- Case Identification: 2:13-cv-02078, D.S.C., 08/13/2013
- Venue Allegations: Plaintiffs allege venue is proper because AstraZeneca commits acts of infringement in the district, is subject to personal jurisdiction in South Carolina, and is involved in separate litigation in the district related to the same accused product.
- Core Dispute: Plaintiffs allege that Defendant’s marketing and sale of the statin drug Crestor® for an anti-inflammatory cardiovascular indication infringes patents directed to methods of using statins to treat inflammatory disorders.
- Technical Context: The technology involves the repurposing of statins—a class of drugs widely used to lower cholesterol—for a new therapeutic use based on their anti-inflammatory properties, specifically to reduce cardiovascular risk in patients who may not have high cholesterol.
- Key Procedural History: The complaint alleges a lengthy pre-suit history, stating that Defendant was notified of Plaintiffs' patent family covering the use of statins for inflammatory diseases as early as June 2003. It further alleges that Plaintiffs specifically warned Defendant that its "JUPITER" clinical trial would infringe the ’800 Patent and that Defendant subsequently refused to take a license. The ’219 Patent is a continuation of the ’800 Patent.
Case Timeline
| Date | Event |
|---|---|
| 1997-11-25 | Priority Date for ’800 and ’219 Patents |
| 2003-01-28 | U.S. Patent No. 6,511,800 Issues |
| 2003-06-01 | Complaint alleges AstraZeneca notified of patent family (approx. date) |
| 2009-12-15 | FDA Advisory Committee meeting on Crestor® "JUPITER Indications" |
| 2010-02-08 | FDA approves Crestor® for "JUPITER Indications" |
| 2013-08-13 | U.S. Patent No. 8,507,219 Issues |
| 2013-08-13 | Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 6,511,800 - “Methods of Treating Nitric Oxide and Cytokine Mediated Disorders”
- Patent Identification: U.S. Patent No. 6511800, “Methods of Treating Nitric Oxide and Cytokine Mediated Disorders,” issued January 28, 2003.
The Invention Explained
- Problem Addressed: The patent background describes conditions involving undesirable or pathological levels of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines, which can cause detrimental inflammation and cell damage in a variety of diseases, including autoimmune disorders, neuroinflammatory conditions, and septic shock ( Compl. ¶8; ’800 Patent, col. 1:11-37).
- The Patented Solution: The invention provides methods for treating these inflammation-mediated disorders by administering an "induction suppressor" that inhibits the cellular pathways responsible for producing iNOS and proinflammatory cytokines. The specification identifies inhibitors of the mevalonate pathway, such as the statin drug lovastatin, as exemplary induction suppressors that can achieve this therapeutic effect (’800 Patent, Abstract; col. 9:35-43).
- Technical Importance: This approach represented a new therapeutic application for an established class of drugs (statins) by targeting their anti-inflammatory properties rather than their well-known lipid-lowering effects (’800 Patent, col. 1:14-20).
Key Claims at a Glance
- The complaint generally asserts "the claims of the ’800 Patent" without specifying any particular claim (Compl. ¶19). Independent claim 1 is representative:
- A method of suppressing the induction of an inducible nitric oxide synthase or a proinflammatory cytokine in a cell,
- comprising contacting said cell with an effective amount of at least one induction suppressor of an inducible nitric oxide synthase or a proinflammatory cytokine.
U.S. Patent No. 8,507,219 - “Method of Treating Inflammation with Statins”
- Patent Identification: U.S. Patent No. 8507219, “Method of Treating Inflammation with Statins,” issued August 13, 2013.
The Invention Explained
- Problem Addressed: As a continuation of the ’800 Patent, the ’219 Patent addresses the same underlying problem of treating inflammation-mediated disorders, with a particular focus on vascular and cardiovascular disease (’219 Patent, Abstract).
- The Patented Solution: The patent claims a more specific method for reducing the risk of cardiovascular disease or stroke in subjects who have elevated inflammation but not necessarily elevated cholesterol. The claimed method involves first determining that a subject has an elevated level of inflammation and then administering an HMG-CoA reductase inhibitor (a statin) to treat that inflammation (’219 Patent, Claim 1).
- Technical Importance: The invention provides a targeted method for using statins as anti-inflammatory agents to prevent cardiovascular events, a therapeutic strategy distinct from their conventional use as cholesterol-lowering drugs (’219 Patent, Claim 1).
Key Claims at a Glance
- The complaint generally asserts "the claims of the ’219 Patent" (Compl. ¶31). Independent claim 1 is representative:
- A method of treating inflammation in cells of a subject that does not have an elevated cholesterol level, to reduce the risk of cardiovascular disease or stroke, the method comprising:
- a) determining the level of inflammation in a subject, or in cells of the subject, which subject does not have an elevated cholesterol level, by testing for an indicator of inflammation;
- b) administering to cells of those subjects determined in step a) to have elevated level of inflammation by virtue of such testing, an amount of an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that is effective to reduce said inflammation and reduce the risk of cardiovascular disease or stroke in said subject.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is the drug Crestor® (rosuvastatin calcium) and its use for certain indications (Compl. ¶10).
Functionality and Market Context
- Crestor® is a drug belonging to the class of statins, which are HMG-CoA reductase inhibitors (Compl. ¶10).
- The complaint focuses on AstraZeneca’s sponsorship of the “JUPITER” clinical trial, which was designed to evaluate whether Crestor® could reduce the risk of cardiovascular disease or stroke in patients who have an indication of inflammation but do not have high cholesterol (Compl. ¶¶11-13).
- Following this trial, the U.S. Food & Drug Administration on February 8, 2010, approved Crestor® for use in preventing heart disease in individuals with "normal" low-density lipoprotein (LDL) cholesterol levels, an indication referred to in the complaint as the "JUPITER Indications" (Compl. ¶¶13, 17). This expanded the drug's approved use beyond its traditional role as a cholesterol-lowering agent.
IV. Analysis of Infringement Allegations
No probative visual evidence provided in complaint.
- ’800 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of suppressing the induction of an inducible nitric oxide synthase or a proinflammatory cytokine in a cell, | AstraZeneca's use of Crestor® in the JUPITER Trial to treat patients with inflammation is alleged to be a method of suppressing inflammation-mediated pathways. | ¶19 | col. 9:35-43 |
| comprising contacting said cell with an effective amount of at least one induction suppressor... | Administration of Crestor®, a statin disclosed in the patent as an exemplary "induction suppressor," to patients in the JUPITER Trial. | ¶19 | col. 9:55-58 |
- ’219 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a) determining the level of inflammation in a subject... by testing for an indicator of inflammation; | AstraZeneca's marketing materials allegedly instruct and encourage doctors to identify patients with an "indication of vascular inflammation" to determine their suitability for Crestor® treatment under the JUPITER Indications. | ¶¶12, 31 | col. 126:5-8 |
| b) administering to cells of those subjects determined in step a) to have elevated level of inflammation... an amount of an inhibitor of... (HMG-CoA) reductase that is effective to reduce said inflammation and reduce the risk of cardiovascular disease or stroke... | AstraZeneca's marketing and promotional materials allegedly instruct and encourage doctors to prescribe Crestor® (an HMG-CoA reductase inhibitor) to the identified patients for the purpose of reducing cardiovascular risk. | ¶¶31-32 | col. 126:9-16 |
- Identified Points of Contention:
- Scope Questions: Claim 1 of the ’219 Patent requires the step of "determining the level of inflammation." A potential point of contention is whether the clinical criteria for identifying patients for the JUPITER Indications, as allegedly promoted by AstraZeneca, meet the legal standard for this claim element.
- Technical Questions: A technical question for the ’800 Patent is whether Crestor® (rosuvastatin) functions as an "induction suppressor" of iNOS or proinflammatory cytokines in the specific manner described in the patent specification for other statins, such as lovastatin. Similarly, for the ’219 Patent, a question is whether the prescribed dose of Crestor® is "effective to reduce said inflammation," a functional limitation that may require evidence beyond simply reducing the ultimate risk of a cardiovascular event.
V. Key Claim Terms for Construction
The Term: "induction suppressor" (’800 Patent)
Context and Importance: This term defines the class of compounds used in the claimed method. Its construction is critical because infringement hinges on whether Crestor® falls within its scope. Practitioners may focus on this term because its definition appears to be functional rather than structural.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a functional definition, stating a "suppressor" is an agent that "produces any measurable reduction in the induction of a gene" (’800 Patent, col. 9:29-33). This language could support a broad construction covering any compound that achieves the stated result, regardless of its specific mechanism.
- Evidence for a Narrower Interpretation: The specification discloses specific examples of induction suppressors, such as lovastatin, and describes their mechanism as inhibitors of the mevalonate synthesis pathway or the Ras/Raf/MAP kinase pathway (’800 Patent, col. 9:44-62). A party might argue that the term should be limited to compounds that operate through these disclosed biological mechanisms.
The Term: "determining the level of inflammation" (’219 Patent)
Context and Importance: This phrase recites an active step required by the method claim. The outcome of the case may depend on whether the diagnostic activities encouraged by AstraZeneca for the JUPITER Indications satisfy this limitation.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The claim language itself is general and does not recite a specific test, biomarker, or quantitative threshold. This may support an argument that a general clinical diagnosis of having an "indication of vascular inflammation" (Compl. ¶12) is sufficient to meet this limitation.
- Evidence for a Narrower Interpretation: The term "determining the level" could be interpreted to require a specific, quantitative measurement of an inflammatory marker rather than a qualitative clinical assessment. The complaint does not provide sufficient detail for analysis of how the level of inflammation was determined in the JUPITER trial beyond a general "indication."
VI. Other Allegations
- Indirect Infringement: The complaint alleges AstraZeneca induced infringement of both patents by encouraging doctors and the public to use Crestor® for the JUPITER Indications (Compl. ¶¶24, 31). This encouragement is alleged to occur through marketing materials, website content, product labeling, and the activities of pharmaceutical sales specialists (Compl. ¶¶24, 26, 31, 33). The complaint alleges AstraZeneca had pre-suit knowledge of the patents and was specifically informed that the JUPITER Trial would infringe (Compl. ¶¶27, 34, 39).
- Willful Infringement: The willfulness allegation is based on alleged pre-suit notice. Plaintiffs claim AstraZeneca was notified of the relevant patent family "as early as June 2003" and was later specifically warned that the JUPITER Trial would infringe the ’800 Patent (Compl. ¶¶38-39). The complaint alleges that despite this notice, AstraZeneca refused to license the patents and proceeded with conduct found to be infringing, thereby acting intentionally and willfully (Compl. ¶¶40, 42).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of infringement theory: The asserted patents claim methods of use, not the Crestor® drug itself. Can Plaintiffs prove that AstraZeneca's acts—first conducting a clinical trial and later marketing the drug for a specific FDA-approved indication—constitute direct and induced infringement of these method claims, especially when direct infringement would be performed by third-party physicians and patients?
- A second central question will be one of claim scope: Can the functional term "induction suppressor" from the ’800 Patent be construed to cover Crestor®, and does the diagnostic step of "determining the level of inflammation" from the ’219 Patent read on the clinical practices promoted by AstraZeneca for the JUPITER Indications?
- Finally, a key issue for damages will be willfulness: Given the allegations of specific, pre-suit notice dating back to 2003, did AstraZeneca proceed with its clinical trial and marketing campaign with an objectively reckless disregard for Plaintiffs' patent rights, or did it have a good-faith belief that the patents were invalid or not infringed?