3:19-cv-12920
Cubist Pharma LLC v. Cipla USA Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Cubist Pharmaceuticals LLC (Switzerland/Delaware)
- Defendant: Cipla USA, Inc. (Delaware/New Jersey) and Cipla Limited (India)
- Plaintiff’s Counsel: Day Pitney LLP; Quinn Emanuel Urquhart & Sullivan, LLP
- Case Identification: 3:19-cv-12920, D.N.J., 05/24/2019
- Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Cipla USA maintains a regular and established place of business in the district, and because Defendant Cipla Limited is a foreign corporation subject to jurisdiction in the district.
- Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market a generic version of Plaintiff's CUBICIN RF® (daptomycin) drug product, constitutes an act of infringement of a patent covering stabilized daptomycin formulations.
- Technical Context: The technology concerns pharmaceutical formulations of the antibiotic daptomycin designed to improve chemical stability and decrease the time required for reconstitution before intravenous administration.
- Key Procedural History: This action was initiated under the Hatch-Waxman Act following Plaintiff's receipt of a notice letter dated April 15, 2019, which included a Paragraph IV certification asserting that the patent-in-suit is invalid, unenforceable, or not infringed by the proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2009-11-23 | ’456 Patent Priority Date |
| 2015-09-22 | ’456 Patent Issue Date |
| 2019-04-15 | Cipla Limited's Paragraph IV Certification Letter Date |
| 2019-05-24 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,138,456 - "Lipopeptide Compositions And Related Methods"
- Patent Identification: U.S. Patent No. 9,138,456, "Lipopeptide Compositions And Related Methods", issued September 22, 2015.
The Invention Explained
- Problem Addressed: The patent describes two problems with prior art daptomycin formulations. First, the lyophilized (freeze-dried) powder could take a long time—15 to 45 minutes—to reconstitute in a liquid diluent before it could be administered to a patient (U.S. Patent No. 9,138,456, col. 1:44-49). Second, daptomycin was susceptible to chemical degradation into structurally similar but undesirable compounds, such as anhydro-daptomycin and a β-isomer, which could impact the product's stability and shelf life (’456 Patent, col. 1:50-col. 2:6).
- The Patented Solution: The invention addresses these problems by creating a new solid formulation of daptomycin. The solution involves adding a sugar, specifically the non-reducing sugar sucrose, to an aqueous solution of daptomycin and then lyophilizing the mixture to create a solid powder (’456 Patent, Abstract; col. 27:2-5). This formulation is described as having both faster reconstitution times and improved chemical stability compared to formulations without the added sugar (’456 Patent, Abstract; col. 3:1-15).
- Technical Importance: For an intravenously administered antibiotic used in serious infections, reducing reconstitution time saves valuable time for healthcare professionals, and improving chemical stability ensures a longer shelf-life and a more reliable product (’456 Patent, col. 2:50-58).
Key Claims at a Glance
- The complaint asserts independent claim 1 and dependent claims 2 and 7-11 (’456 Patent, col. 27:2-col. 28:11; Compl. ¶31).
- The essential elements of independent claim 1 are:
- A solid pharmaceutical daptomycin composition,
- wherein said composition is prepared by lyophilizing an aqueous daptomycin solution comprising daptomycin and sucrose.
- The complaint reserves the right to assert additional claims (’456 Patent, col. 27:6-col. 28:38).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Cipla's Proposed ANDA Product," which is a generic version of "Daptomycin for Injection, 500 mg per vial" intended to be a substitute for Plaintiff's CUBICIN RF® drug product (Compl. ¶¶ 1, 25).
Functionality and Market Context
The complaint alleges that this is a pharmaceutical product for treating complicated skin and skin structure infections and certain bloodstream infections (Compl. ¶6). The act of infringement alleged is the filing of ANDA No. 213027 with the FDA, which seeks approval to commercially manufacture and sell this generic product in the United States prior to the expiration of the ’456 patent (Compl. ¶¶ 1, 30). The complaint alleges that the '456 patent is listed in the FDA's "Orange Book" with respect to CUBICIN RF®, putting would-be generic manufacturers on notice (Compl. ¶8). No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not contain a claim chart or specific factual allegations mapping elements of the accused product to the patent claims. The infringement theory appears to be that in order to be a bioequivalent generic of CUBICIN RF®, which is covered by the Orange Book-listed ’456 patent, the Defendants' proposed product must necessarily have the composition claimed in the patent.
’456 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A solid pharmaceutical daptomycin composition, | The complaint identifies the accused instrumentality as "Cipla's Proposed ANDA Product," a generic version of "Daptomycin for Injection, 500 mg per vial," which is a solid pharmaceutical daptomycin composition. | ¶¶1, 25 | col. 27:2-3 |
| wherein said composition is prepared by lyophilizing an aqueous daptomycin solution comprising daptomycin and sucrose. | The complaint alleges on information and belief that discovery will show Cipla's Proposed ANDA Product infringes, which suggests an assertion that the product's formulation contains sucrose and is prepared via lyophilization to achieve the required characteristics of the branded drug. | ¶¶26, 31 | col. 27:3-5 |
Identified Points of Contention
- Factual Question: The central dispute will likely be factual: what is the precise formulation of Cipla’s Proposed ANDA Product? The complaint does not provide, and may not yet possess, direct evidence that the accused product contains sucrose. The case may turn on whether discovery reveals the presence of sucrose in Cipla's formulation.
- Scope Question: A key legal and technical question concerns the "prepared by lyophilizing" limitation. The court will have to determine whether this product-by-process claim is infringed only if Cipla uses the same lyophilization process, or if it is infringed if Cipla's product, regardless of the process used, has the same structural and functional characteristics as a product made by the claimed process.
V. Key Claim Terms for Construction
The Term: "prepared by lyophilizing"
Context and Importance: This term makes Claim 1 a "product-by-process" claim. The construction of this term is critical because it will determine the nature of proof Cubist must provide. Practitioners may focus on this term because its interpretation will define whether the infringement analysis centers on Cipla's actual manufacturing method or solely on the characteristics of its final drug product.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification mentions that the solid composition can be prepared by various methods, including "lyophilization, spray-drying or the like" (’456 Patent, col. 2:65-col. 3:1). This could support an argument that the claim covers any solid daptomycin-sucrose composition that has the properties (e.g., stability, reconstitution time) imparted by the lyophilization process, even if made by another method.
- Evidence for a Narrower Interpretation: The claim language itself explicitly recites "lyophilizing" (’456 Patent, col. 27:3). The patent provides detailed exemplary lyophilization cycles, including specific temperatures, pressures, and durations, which could be argued to define the scope of the claimed process (’456 Patent, Table 2, col. 16:1-38). This may support an argument that the process itself is a hard limit on claim scope.
The Term: "sucrose"
Context and Importance: The addition of sucrose is presented as the key inventive step to solve the prior art's problems. Whether Cipla's product contains sucrose will likely be a dispositive issue for infringement of claim 1.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes sucrose as a preferred example of a "non-reducing sugar" and lists other sugars like trehalose and mannitol as also being suitable for improving stability and reconstitution (’456 Patent, col. 3:5-10; col. 4:15-21). This could be used to support an argument under the doctrine of equivalents if Cipla's product uses a different, but functionally similar, non-reducing sugar.
- Evidence for a Narrower Interpretation: Claim 1 specifically and narrowly recites "sucrose" without referencing other sugars (’456 Patent, col. 27:5). The abstract also highlights sucrose specifically, stating "Some examples of the compositions comprise daptomycin and sucrose" (’456 Patent, Abstract). This provides a basis for arguing that the claim is limited to formulations containing only sucrose, not other sugars.
VI. Other Allegations
Indirect Infringement
The complaint alleges that Defendants will induce and contribute to infringement by commercially manufacturing, using, selling, or importing the Proposed ANDA Product with the knowledge and intent that it be used for the same FDA-approved indications as the branded CUBICIN RF® product (Compl. ¶¶ 12, 31).
Willful Infringement
The complaint alleges that Cipla has had knowledge of the '456 patent since at least the date it submitted the ANDA, which included a Paragraph IV certification against the patent (Compl. ¶32). This alleged pre-suit knowledge forms the basis for a potential willfulness claim.
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of compositional fact: what is the actual chemical composition of Cipla's Proposed ANDA Product? As the complaint provides no direct evidence, the case will hinge on whether discovery reveals that the generic formulation contains sucrose, as literally required by the asserted independent claim.
- A key legal question will be one of claim construction: how will the court construe the "prepared by lyophilizing" limitation? The resolution of whether this requires proof of Cipla's manufacturing process, or merely proof that Cipla's final product has the characteristics imparted by that process, will significantly shape the scope of discovery and the evidence required for a finding of infringement.