DCT
3:07-cv-02762
Sanofi Aventis US LLC v. Sandoz Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Sanofi-Aventis U.S. LLC (Delaware), Sanofi-Aventis (France), and Debiopharm, S.A. (Switzerland)
- Defendant: Sandoz, Inc. (Colorado)
- Plaintiff’s Counsel: McCarter & English, LLP; Fitzpatrick, Cella, Harper & Scinto
- Case Identification: 3:07-cv-02762, D.N.J., 06/14/2007
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Sandoz, Inc. has a principal place of business in Princeton, New Jersey, and regularly conducts business in the district.
- Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug Eloxatin® constitutes an act of patent infringement.
- Technical Context: The patents-in-suit relate to the anti-cancer compound oxaliplatin, specifically claiming an optically pure version of the molecule and a stable, ready-to-use aqueous formulation for injection.
- Key Procedural History: This is a Hatch-Waxman action triggered by Sandoz’s filing of ANDA No. 78-817 with the FDA. The ANDA included a Paragraph IV certification, asserting that Plaintiffs’ patents are invalid and/or not infringed by Sandoz’s proposed generic product. This certification is the statutory act of infringement giving rise to the lawsuit.
Case Timeline
| Date | Event |
|---|---|
| 1993-01-12 | ’874 Patent Priority Date |
| 1994-08-08 | ’988 Patent Priority Date |
| 1994-08-16 | ’874 Patent Issue Date |
| 1998-02-10 | ’988 Patent Issue Date |
| 2007-06-14 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 5,338,874 - "CIS OXALATO (TRANS 1-1,2-CYCLOHEXANEDIAMINE) PT(II) HAVING OPTICALLY HIGH PURITY," issued August 16, 1994
The Invention Explained
- Problem Addressed: The patent’s background explains that while platinum complexes of 1,2-cyclohexanediamine were known to have anti-cancer activity, they were typically synthesized as a mixture of optical isomers (trans-d and trans-l) (’874 Patent, col. 1:11-18). The patent notes that for many drugs, different optical isomers can have significant differences in therapeutic activity and side effects, making optical purity especially important (’874 Patent, col. 1:55-59). Conventionally reported methods for isolating the desired isomer were deemed "insufficient," leaving the purity of the resulting compound in question (’874 Patent, col. 1:50-54).
- The Patented Solution: The invention is the specific, "optically high purity" form of the trans-l isomer of the platinum complex, also known as oxaliplatin (’874 Patent, col. 2:3-6). The specification describes a purification and analysis process, including High-Performance Liquid Chromatography (HPLC), capable of separating the desired isomer from its counterpart and yielding a product of 100% optical purity (’874 Patent, col. 4:62-66). This highly pure compound is asserted to be more effective and safer as a medicine compared to the previously known mixtures (’874 Patent, col. 2:21-29).
- Technical Importance: The invention provided a composition of matter for a highly pure, single-isomer version of a promising anti-cancer agent, which is critical for consistent therapeutic effect and minimizing toxicity associated with unwanted isomers.
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent (’874 Patent, ¶17).
- Independent Claim 1:
- Optically pure cis-oxalato (trans-1-1,2-cyclohexanediamine) Pt(II)
- having a general formula of Formula (1).
U.S. Patent No. 5,716,988 - "PHARMACEUTICALLY STABLE PREPARATION OF OXALIPLATINUM," issued February 10, 1998
The Invention Explained
- Problem Addressed: The patent states that oxaliplatin was previously available as a lyophilisate, or a freeze-dried powder, which had to be reconstituted with a liquid (e.g., injectable water or glucose solution) just before administration (’988 Patent, col. 1:31-36). This process is described as "relatively complicated and expensive" and carries a "risk of an error being made when reconstituting," such as using an incorrect saline solution that would cause the drug to precipitate and degrade (’988 Patent, col. 1:39-53).
- The Patented Solution: The invention is a "ready to use" aqueous solution of oxaliplatin that is "pharmaceutically stable" for an extended duration, eliminating the need for lyophilization and reconstitution (’988 Patent, col. 1:57-64). The stability is achieved by controlling two key parameters: the concentration of oxaliplatin in water (1 to 5 mg/ml) and the pH of the solution (4.5 to 6) (’988 Patent, Abstract; col. 2:9-14).
- Technical Importance: This invention provided a safer, more convenient, and less error-prone dosage form for administering oxaliplatin, improving its practicality in a clinical setting.
Key Claims at a Glance
- The complaint asserts "one or more claims" of the patent (’988 Patent, ¶24).
- Independent Claim 1:
- A pharmaceutically stable preparation of oxaliplatinum for administration by the parenteral route,
- consisting of a solution of oxaliplatinum in water at a concentration of 1 to 5 mg/ml,
- and having a pH of 4.5 to 6,
- the oxaliplatinum content in the preparation being at least 95% of the initial content and the solution remaining clear, colorless and free of precipitate after storage for a pharmaceutically acceptable duration of time.
III. The Accused Instrumentality
- Product Identification: The accused instrumentality is Sandoz's proposed generic drug product, "oxaliplatin solution for injection in 50 mg vial (5 mg/ml) and 100 mg vial (5 mg/ml) formulations," which is the subject of ANDA No. 78-817 (Compl. ¶6).
- Functionality and Market Context: The Sandoz product is a proposed generic copy of Plaintiffs' Eloxatin®, an approved treatment for colorectal cancer whose active ingredient is oxaliplatin (Compl. ¶5, ¶11). As an "oxaliplatin solution for injection," its function is to provide a ready-to-use formulation of the anti-cancer drug for parenteral administration (Compl. ¶6, ¶13). The complaint notes that at the time of filing, there were no FDA-approved generic oxaliplatin products available for sale in the United States (Compl. ¶11). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint alleges that the act of filing the ANDA to seek approval for the generic product constitutes infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶16, ¶23).
’874 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| Optically pure cis-oxalato (trans-1-1,2-cyclohexanediamine) Pt(II) having a general formula of Formula (1). | The active ingredient of the innovator drug Eloxatin® is oxaliplatin. To be a generic equivalent, Sandoz’s proposed product as described in its ANDA must contain the same active ingredient. | ¶6, ¶11 | col. 2:3-12 |
- Identified Points of Contention:
- Scope Questions: A central dispute may concern the meaning of "Optically pure." The defense may argue that its product does not meet the specific, high standard of purity required by the patent, or that the term is indefinite. The patent’s examples describe achieving "100% of an optical purity (e.e.)" (’874 Patent, col. 4:65-66), which may support a narrow construction that Sandoz could design around or argue it does not meet.
’988 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| a solution of oxaliplatinum in water | The accused product is an "oxaliplatin solution for injection". | ¶6 | col. 2:2-4 |
| at a concentration of 1 to 5 mg/ml | The accused product is described as having formulations of "50 mg vial (5 mg/ml) and 100 mg vial (5 mg/ml)". | ¶6 | col. 2:11-12 |
| and having a pH of 4.5 to 6 | The complaint does not provide sufficient detail for analysis of this element. | col. 2:12-13 | |
| the oxaliplatinum content in the preparation being at least 95% of the initial content and the solution remaining clear, colorless and free of precipitate after storage for a pharmaceutically acceptable duration of time | As a stable solution submitted for FDA approval, the Sandoz product must meet regulatory stability requirements, which are alleged to fall within this limitation. | ¶16, ¶23 | col. 2:14-18 |
- Identified Points of Contention:
- Technical Questions: Does the Sandoz formulation, as described in its confidential ANDA, possess a pH that falls within the claimed 4.5 to 6 range? The complaint does not allege a specific pH for the accused product, making this a key factual question for discovery.
- Scope Questions: What constitutes a "pharmaceutically acceptable duration of time" for stability? The claim language is functional, but the specification provides an example of "3 to 5 years at room temperature" (’988 Patent, col. 2:30-33), which could be used to argue for a specific temporal scope for this limitation.
V. Key Claim Terms for Construction
For the ’874 Patent
- The Term: "Optically pure"
- Context and Importance: This term is the primary distinction between the claimed invention and the prior art mixtures of isomers. Its construction will likely determine whether the ’874 Patent is valid over the prior art and infringed by the Sandoz product. Practitioners may focus on this term because its definition dictates the required level of isomeric purity for infringement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Narrower Interpretation: The patent repeatedly emphasizes achieving complete separation and purity. The examples state that after HPLC resolution, the product has "100% of an optical purity (e.e.)" (’874 Patent, col. 4:65-66). Table 1, titled "Optical Purity," lists the "After Resolution" purity as "100" for all three examples (’874 Patent, Table 1). This could support an argument that "optically pure" means complete or near-complete absence of the other isomer.
- Evidence for a Broader Interpretation: The "Summary of the Invention" states an object is to provide a compound of "high purity" (’874 Patent, col. 1:63-66). The background contrasts the invention with "insufficient" isolation in prior art (’874 Patent, col. 1:52). This could support an argument that "optically pure" should be construed not as absolutely pure, but as having a purity level substantially higher than and different from the prior art mixtures, sufficient to achieve the stated safety benefits.
For the ’988 Patent
- The Term: "pharmaceutically acceptable duration of time"
- Context and Importance: This term defines the stability requirement of the claimed formulation. Its temporal scope is critical for the infringement analysis, as Sandoz's ANDA will contain stability data for a specific shelf life. Practitioners may focus on this term to determine if standard FDA-mandated shelf-life data (e.g., for 24 months) meets the claimed requirement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Narrower Interpretation: The detailed description provides a specific example of the duration, stating that the preparation must remain stable "for example during 3 to 5 years at room temperature" (’988 Patent, col. 2:31-33). Plaintiffs may argue this language defines the minimum acceptable duration.
- Evidence for a Broader Interpretation: A party could argue the "3 to 5 years" language is merely an example ("i.e. for example") and not a limiting definition. The claim uses the broader term "pharmaceutically acceptable," which could be interpreted as any duration sufficient to meet regulatory standards for an approved, marketable drug product, which might be shorter than 3 years.
VI. Other Allegations
- Indirect Infringement: The complaint does not contain specific factual allegations to support claims of induced or contributory infringement. The primary allegation is direct infringement under 35 U.S.C. § 271(e)(2) based on the ANDA filing, with an additional allegation that future commercial activity will constitute direct infringement under 35 U.S.C. § 271 (Compl. ¶16, ¶17, ¶23, ¶24).
- Willful Infringement: The complaint does not explicitly allege "willful" infringement. However, it requests a declaration that the case is "exceptional" under 35 U.S.C. § 285 and seeks an award of attorney fees (Compl., Prayer for Relief ¶D). The factual basis for this request is the allegation that Sandoz filed an ANDA with a Paragraph IV certification, which necessarily requires knowledge of the asserted patents.
VII. Analyst’s Conclusion: Key Questions for the Case
This litigation appears to center on classic ANDA-related disputes of claim scope and evidentiary proof. The key questions raised by the complaint are:
A core issue will be one of definitional scope: For the ’874 patent, what level of isomeric separation does the term "Optically pure" require? The case may turn on whether this term demands the 100% enantiomeric excess shown in the patent's examples or allows for a lesser, albeit high, degree of purity.
A key evidentiary question will be one of factual compliance: For the ’988 patent, does Sandoz's proposed generic formulation, as confidentially described in its ANDA, meet every limitation of the asserted claims? Specifically, discovery will focus on whether the product's pH falls within the claimed 4.5 to 6 range and whether its stability data satisfies the "pharmaceutically acceptable duration" required by the claim.