DCT

1:20-cv-00052

Cubist Pharma LLC v. Mylan Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00052, N.D.W. Va., 07/13/2020
  • Venue Allegations: Venue is alleged based on Defendant Mylan Pharmaceuticals Inc. being a West Virginia corporation with a place of business in the district, and other Mylan entities allegedly having places of business and intending to commit acts of infringement in the district.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) for a generic version of the antibiotic drug CUBICIN RF® constitutes an act of infringement of patents related to stable daptomycin compositions and methods of making them.
  • Technical Context: The technology concerns pharmaceutical formulations of daptomycin, an antibiotic, designed to improve chemical stability and reduce the time required for reconstitution before intravenous administration.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following Plaintiff's receipt on or about February 19, 2020, of a notice letter regarding Defendants' ANDA No. 213966, which included a Paragraph IV certification alleging the patents-in-suit are invalid, unenforceable, and/or not infringed.

Case Timeline

Date Event
2009-11-23 Priority Date for ’382 and ’456 Patents
2014-09-16 U.S. Patent No. 8,835,382 Issues
2015-09-22 U.S. Patent No. 9,138,456 Issues
2020-02-19 Date of Mylan's ANDA Notice Letter to Cubist
2020-07-13 Complaint Filing Date

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

U.S. Patent No. 9,138,456 - Lipopeptide Compositions And Related Methods (Issued Sep. 22, 2015)

  • The Invention Explained:
    • Problem Addressed: The patent's background section describes two technical problems with existing solid daptomycin formulations: slow reconstitution time in a pharmaceutical diluent, which can take 15-45 minutes, and the need for improved chemical stability to ensure a longer shelf life and tolerance for varied storage conditions (’456 Patent, col. 2:38-57).
    • The Patented Solution: The invention is a solid pharmaceutical composition of daptomycin that includes sucrose. This formulation is created by lyophilizing (freeze-drying) an aqueous solution containing both daptomycin and sucrose, a process which results in a solid product that reconstitutes more rapidly and exhibits greater chemical stability than formulations without sucrose (’456 Patent, Abstract; col. 3:55-66).
    • Technical Importance: The patented solution provides a clinically meaningful advantage by reducing the preparation time for an important antibiotic, while also improving the product's shelf life and robustness (’456 Patent, col. 2:50-57).
  • Key Claims at a Glance:
    • Independent Claim 1:
      • A solid pharmaceutical daptomycin composition,
      • wherein said composition is prepared by lyophilizing an aqueous daptomycin solution
      • comprising daptomycin and sucrose.
    • The complaint also asserts dependent claims 2 and 7-11, which add limitations such as specific molar ratios, the inclusion of a buffering agent, and the pH of the pre-lyophilized aqueous solution, as well as claim 15, which covers a specific formulation prepared by a defined process (Compl. ¶¶40, 45).

U.S. Patent No. 8,835,382 - Lipopeptide Compositions And Related Methods (Issued Sep. 16, 2014)

  • The Invention Explained:
    • Problem Addressed: The patent addresses the same technical challenges as the ’456 Patent: the slow reconstitution and chemical instability of prior art daptomycin formulations (’382 Patent, col. 2:38-57).
    • The Patented Solution: The invention claims a method for manufacturing the improved daptomycin preparation. The method involves forming an aqueous solution that contains both daptomycin and sucrose, adjusting that solution to a specific pH range of about 6.5 to 7.5, and then converting the solution into a solid form, for example through lyophilization (’382 Patent, Abstract; col. 28:1-4). This process yields the stable, fast-reconstituting solid composition.
    • Technical Importance: This patent protects the specific manufacturing process required to create the improved daptomycin product, providing a different layer of protection from the product patent.
  • Key Claims at a Glance:
    • Independent Claim 1:
      • A method of manufacturing a pharmaceutical daptomycin preparation,
      • comprising forming an aqueous daptomycin solution comprising daptomycin and sucrose at a pH of about 6.5-7.5,
      • and converting the aqueous daptomycin solution to a solid pharmaceutical daptomycin preparation.
    • The complaint also asserts dependent claims 2-3 and 5-15, which further define the method with limitations such as specific molar ratios, excipients, and conversion techniques, along with independent claims 17-18, which cover related methods (Compl. ¶¶35, 50).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is "Mylan’s Proposed ANDA Product," a generic version of Plaintiff's CUBICIN RF® (daptomycin for injection) drug product, for which Defendants seek FDA approval via ANDA No. 213966 (Compl. ¶¶1, 31).
  • Functionality and Market Context: The proposed product is an antibiotic for treating complicated skin and skin structure infections and certain bloodstream infections (Compl. ¶9). The act of infringement alleged is the submission of the ANDA itself, which seeks approval to manufacture, use, and sell the generic drug in the United States before the expiration of the patents-in-suit (Compl. ¶¶36, 39). The complaint also alleges infringement based on the method by which the product is manufactured in India for importation into the United States (Compl. ¶¶35, 51).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide sufficient detail for a tabular claim chart analysis. The infringement theory is summarized below.

  • ’456 Patent Infringement Theory: The complaint alleges that Mylan’s submission of its ANDA is an act of infringement under 35 U.S.C. § 271(e)(2) (Compl. ¶39). It further alleges, upon information and belief, that if Mylan commercially manufactures or sells its Proposed ANDA Product, that product will infringe claims covering solid pharmaceutical daptomycin compositions (Compl. ¶40). The complaint states that discovery will show infringement of at least claims 1-2, 7-11, and 15, which suggests an allegation that the proposed generic product is a solid daptomycin composition containing sucrose and prepared by lyophilization (Compl. ¶40).
  • ’382 Patent Infringement Theory: The complaint alleges that Defendants have developed and used an infringing method to prepare batches of the Proposed ANDA Product and that the future commercial manufacture of the product using this method will infringe the ’382 patent (Compl. ¶¶48-49). It asserts that discovery will show that the method by which the product is manufactured infringes at least claims 1-3, 5-15, and 17-18 of the ’382 patent, suggesting an allegation that Mylan's process involves creating a daptomycin-sucrose solution at a specific pH before converting it to a solid (Compl. ¶35).
  • Identified Points of Contention:
    • Factual Questions (Composition): A central question for the ’456 Patent will be factual: Does the formulation described in Mylan's ANDA contain sucrose as required by claim 1, or another excipient whose properties might raise questions of equivalence?
    • Factual Questions (Process): For the ’382 Patent, the dispute will likely concern the specifics of the manufacturing process in Mylan's ANDA. Does that process involve forming an aqueous solution of daptomycin and sucrose within the claimed pH range of "about 6.5-7.5" before solidification?

V. Key Claim Terms for Construction

  • The Term: "sucrose" (from ’456 Patent, claim 1)
    • Context and Importance: This term defines a required excipient in the claimed composition. The infringement analysis for the ’456 Patent will depend entirely on whether Mylan's Proposed ANDA Product contains sucrose. If it contains a different sugar, the construction of this term—and potential arguments regarding the doctrine of equivalents—will be critical.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification discusses sugars as a class for improving reconstitution and stability and provides examples using other non-reducing sugars like trehalose and mannitol, which could be used to argue that "sucrose" is exemplary of a functional class of sugars (’456 Patent, col. 3:45-53).
      • Evidence for a Narrower Interpretation: Claim 1 explicitly recites "sucrose" without broader generic language. Other claims and embodiments in the patent family also specifically name other sugars, which may support an interpretation that when the patentee said "sucrose," they meant only that specific disaccharide.
  • The Term: "at a pH of about 6.5-7.5" (from ’382 Patent, claim 1)
    • Context and Importance: This phrase defines a critical process parameter in the claimed manufacturing method. Whether Mylan's process infringes may depend on the precise pH used and the scope afforded by the word "about." Practitioners may focus on this term because small variations in manufacturing processes are common, and the boundaries of this claimed range will be a central point of dispute.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The use of the word "about" itself suggests the range is not absolute and encompasses values close to the stated endpoints. The patent's general disclosure emphasizes the benefit of lyophilizing from a near-neutral pH (e.g., about 7.0) compared to a more acidic pH (e.g., 4.7), which may support interpreting the range functionally to include any pH that achieves the stated benefits of stability and fast reconstitution (’382 Patent, col. 3:4-9).
      • Evidence for a Narrower Interpretation: The specification provides numerous examples with formulations prepared at a pH of 7.0, which falls squarely within the claimed range (’382 Patent, Table 6). A defendant may argue that the term "about" only covers minor experimental variability and that a process operating at a pH meaningfully outside 6.5-7.5, even if near-neutral, is non-infringing.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that the various Mylan defendants will work in concert to make, use, sell, or import the accused product, and that this conduct will induce or contribute to infringement of the patents-in-suit (Compl. ¶¶34, 40, 50).
  • Willful Infringement: The complaint does not contain an explicit claim for willful infringement. However, it alleges that Mylan has had knowledge of the ’456 patent since at least the date it submitted its ANDA and of the ’382 patent since at least the date of its February 19, 2020 notice letter (Compl. ¶¶41, 52). These allegations could form the basis for a later claim for enhanced damages.

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

The resolution of this case will likely depend on the answers to two primary factual questions, the details of which reside in the confidential ANDA filing.

  • A core issue will be one of compositional identity: Does Mylan's proposed generic daptomycin product contain sucrose, as explicitly required by the asserted claims of the ’456 Patent? If not, the case will shift to a more complex dispute over the doctrine of equivalents.
  • A parallel issue will be one of process identity: Does the manufacturing method described in Mylan's ANDA meet the specific parameters of the ’382 Patent's method claims, particularly the requirement to form the daptomycin-sucrose solution "at a pH of about 6.5-7.5" prior to converting it into a solid?