1:09-cv-00750
Medicines Co v. Hospira Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: The Medicines Company (Delaware)
- Defendant: Teva Parenteral Medicines, Inc. (Delaware); Teva Pharmaceuticals USA, Inc. (Delaware); Teva Pharmaceutical Industries, Ltd. (Israel)
- Plaintiff’s Counsel: Richards, Layton & Finger P.A.; Frommer Lawrence & Haug LLP
- Case Identification: 1:09-cv-00750, D. Del., 10/08/2009
- Venue Allegations: Venue is alleged to be proper based on the Delaware incorporation of two defendant entities (Teva Parenteral and Teva USA) and the alleged continuous and systematic contacts of the foreign parent (Teva Ltd.) with the state through its U.S. subsidiaries.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) seeking FDA approval to market a generic version of the anticoagulant drug bivalirudin constitutes an act of infringement of a patent covering high-purity pharmaceutical formulations of that drug.
- Technical Context: The technology concerns pharmaceutical compounding methods designed to minimize the formation of specific chemical impurities in bivalirudin formulations, thereby improving product stability and shelf-life.
- Key Procedural History: This action arises under the Hatch-Waxman Act, triggered by Defendant Teva Parenteral's filing of ANDA No. 90-748 with a Paragraph IV certification. The certification alleges that U.S. Patent No. 7,582,727, which is listed in the FDA's "Orange Book" for Plaintiff's Angiomax® product, is invalid or will not be infringed by Teva's proposed generic product. The complaint notes that Teva refused to provide Plaintiff with access to its ANDA or product samples prior to litigation.
Case Timeline
| Date | Event |
|---|---|
| 2008-07-27 | '727 Patent Priority Date |
| 2009-09-01 | '727 Patent Issue Date |
| 2009-10-08 | Complaint Filing Date |
| 2010-09-23 | Expected FDA Approval Date for Teva's ANDA (Alleged) |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,582,727 - "Pharmaceutical formulations of bivalirudin and processes of making the same," Issued September 1, 2009
The Invention Explained
- Problem Addressed: The patent’s background section explains that while bivalirudin is a highly effective anticoagulant, the process of compounding it into a stable pharmaceutical formulation can generate significant impurities, particularly Asp⁹-bivalirudin. The formation of this impurity, which can reach up to 12% in some processes, may negatively affect the product's stability and shelf-life (’727 Patent, col. 2:7-21).
- The Patented Solution: The invention is a compounding process and the resulting high-purity formulation. The process involves dissolving bivalirudin and then "efficiently mixing" it with a pH-adjusting solution. This controlled mixing process is designed to minimize the formation of localized "hot spots" of high pH, which are believed to accelerate the degradation of bivalirudin into the Asp⁹-bivalirudin impurity (’727 Patent, col. 2:32-38; col. 9:20-33). The result is a pharmaceutical product characterized by a very low level of this specific impurity.
- Technical Importance: By controlling the formation of degradation products during manufacturing, the invention enables the consistent production of a more stable and pure bivalirudin drug product, which is essential for ensuring quality and efficacy in therapeutic applications (’727 Patent, col. 2:2-7).
Key Claims at a Glance
- The complaint alleges infringement of "one or more claims" but does not specify which ones (Compl. ¶29). Independent claim 1 is a representative product claim.
- The essential elements of independent claim 1 are:
- Pharmaceutical batches of a drug product comprising bivalirudin (SEQ ID NO: 1) and a pharmaceutically acceptable carrier
- for use as an anticoagulant in a subject in need thereof,
- wherein the batches have a pH adjusted by a base,
- said pH is about 5-6 when reconstituted in an aqueous solution for injection,
- and wherein the batches have a maximum impurity level of Asp⁹-bivalirudin that does not exceed about 0.6% as measured by HPLC.
- The complaint does not foreclose the assertion of other independent claims (e.g., 11 and 19) or any dependent claims.
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Teva's Proposed Product," a generic bivalirudin formulation (250 mg/vial, for intravenous injection) that is the subject of Teva's ANDA No. 90-748 (Compl. ¶18).
Functionality and Market Context
The product is a generic equivalent of Plaintiff's Angiomax® drug and is intended for use as an anticoagulant in patients (Compl. ¶¶15, 18). The complaint alleges that upon receiving FDA approval, which it anticipates on or about September 23, 2010, Defendants will commercially manufacture, use, and sell this product in the United States (Compl. ¶27). The complaint does not contain specific technical details about the composition or manufacturing process of Teva's product, noting that Plaintiff's request for access to the ANDA was refused (Compl. ¶23).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint, filed under the provisions of the Hatch-Waxman Act, does not provide a detailed breakdown of its infringement theory, as is common in such initial pleadings. The infringement allegations are made on information and belief pending discovery and access to the confidential ANDA materials (Compl. ¶30).
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Pharmaceutical batches of a drug product comprising bivalirudin (SEQ ID NO: 1) and a pharmaceutically acceptable carrier for use as an anticoagulant... | Teva's Proposed Product is a drug product containing bivalirudin for use as an anticoagulant. | ¶18 | col. 25:56-60 |
| ...wherein the batches have a pH adjusted by a base, said pH is about 5-6 when reconstituted in an aqueous solution for injection... | The complaint alleges that Teva's Proposed Product, which is the subject of ANDA No. 90-748, will have the characteristics of the claimed invention. The specific pH upon reconstitution is not detailed. | ¶30 | col. 26:1-5 |
| ...and wherein the batches have a maximum impurity level of Asp⁹-bivalirudin that does not exceed about 0.6% as measured by HPLC. | The complaint alleges on information and belief that Teva's Proposed Product will infringe, which implies that its impurity profile will meet this limitation. The factual basis for this is contained within the confidential ANDA. | ¶30 | col. 26:5-8 |
- Identified Points of Contention:
- Evidentiary Question: The central dispute will be evidentiary. Does Teva's proposed generic product, as described in its confidential ANDA and as it would be commercially manufactured, in fact meet the claimed limitations? Specifically, discovery will focus on whether Teva's product consistently exhibits an Asp⁹-bivalirudin level that "does not exceed about 0.6%" and a reconstituted pH of "about 5-6."
- Scope Question: The interpretation of the word "about" in the claim limitations "about 5-6" and "about 0.6%" will be critical. The court will need to determine the numerical range encompassed by this term, which will directly impact the infringement analysis.
V. Key Claim Terms for Construction
The Term: "maximum impurity level of Asp⁹-bivalirudin that does not exceed about 0.6%"
Context and Importance: This term is the central feature distinguishing the claimed invention. The outcome of the infringement analysis depends almost entirely on whether Teva's product falls within the scope of this limitation. Practitioners may focus on this term because the definition of "about" could be dispositive.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification discusses a hierarchy of impurity levels, including claims that recite levels not exceeding 1.5% or 1%, which could suggest that "about 0.6%" is not an absolute ceiling and allows for some variability ('727 Patent, col. 12:44-47).
- Evidence for a Narrower Interpretation: The patent repeatedly emphasizes the achievement of low impurity levels as a key advantage over prior art processes. Example 5, which describes the preferred embodiment of the process, resulted in batches with a mean Asp⁹-bivalirudin level of 0.3% and a maximum of 0.6% ('727 Patent, Table 7, col. 23). This data may be used to argue that "about 0.6%" should be construed narrowly to mean 0.6% or a level very close to it.
The Term: "pharmaceutical batches"
Context and Importance: The claims are directed to "batches" of a drug product. The parties may dispute whether the claimed purity and reconstitution characteristics must be met by every single manufactured batch or if the limitation can be satisfied by an average or representative sample.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party could argue that in the context of large-scale pharmaceutical manufacturing, the term "batches" implies adherence to a specification that may allow for some statistical variation or outliers.
- Evidence for a Narrower Interpretation: The specification uses the phrase "consistently generate pharmaceutical batches" and "consistently having a maximum impurity level," which suggests that the invention's benefit is its reliability and uniformity across production runs. This language could support an interpretation that every batch must meet the claimed criteria ('727 Patent, col. 13:10-14, col. 13:28-31).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Teva USA and Teva Ltd. are liable for induced and contributory infringement. The allegations are based on their purported roles in actively inducing, encouraging, and aiding Teva Parenteral's preparation and submission of the ANDA with the Paragraph IV certification (Compl. ¶¶35-37).
- Willful Infringement: Plaintiff alleges that all Defendants were aware of the '727 patent but "acted without a reasonable basis for believing" they would not be liable for infringement. This allegation forms the basis for a claim of willful infringement and a request for a finding that the case is "exceptional" under 35 U.S.C. § 285, which would permit an award of attorneys' fees (Compl. ¶¶31, 39).
VII. Analyst’s Conclusion: Key Questions for the Case
A central issue will be one of evidence and testing: As the technical details of the accused product are contained in a confidential ANDA, the case will depend on discovery to reveal whether Teva’s proposed generic product, when manufactured and tested, actually demonstrates the specific chemical properties required by the patent claims—most critically, an Asp⁹-bivalirudin impurity level that does not exceed "about 0.6%."
The dispute will likely involve a significant question of claim construction and definitional scope: The court's interpretation of the term "about" as it modifies the numerical purity and pH limitations in the claims will be critical. Whether "about 0.6%" creates a bright-line rule or allows for a measurable degree of tolerance will likely define the boundary between infringement and non-infringement.