DCT

1:22-cv-01196

BioDelivery Sciences Intl Inc v. Chemo Research SL

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:22-cv-01196, D. Del., 09/12/2022
  • Venue Allegations: Plaintiffs allege venue is proper because Defendants consented to venue in the district in a related case involving the same Abbreviated New Drug Application (ANDA), parties, and patents.
  • Core Dispute: Plaintiffs allege that Defendants’ submission of an ANDA to market a generic version of the opioid pain medication Belbuca® (buprenorphine buccal film) constitutes an act of infringement of three U.S. patents.
  • Technical Context: The technology concerns transmucosal drug delivery systems, specifically bioerodable films designed to enhance the absorption of buprenorphine through the oral mucosa for pain management.
  • Key Procedural History: This action is related to a prior case, C.A. No. 19-444-CFC (D. Del.), involving the same parties and the same ANDA. In that prior case, the parties entered into a stipulation, dated February 26, 2021, that precludes Defendants from asserting any validity challenges against the patents-in-suit in this or any subsequent action concerning the ANDA. This history suggests the current dispute will focus exclusively on infringement, not patent validity.

Case Timeline

Date Event
2006-07-21 Earliest Priority Date for '866 & '843 Patents
2011-12-21 Priority Date for '539 Patent
2012-04-03 '866 Patent Issued
2015-10-23 FDA Approved NDA for Belbuca®
2017-05-23 '843 Patent Issued
2018-02-27 '539 Patent Issued
2018-01-01 Defendants Filed Original ANDA No. 212036 (stated as "in 2018")
2021-02-26 Stipulation Precluding Validity Challenges
2022-07-29 Defendants Sent Notice Letter for Amended ANDA
2022-09-12 Complaint Filed

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

U.S. Patent No. 8,147,866 - "Transmucosal Delivery Devices with Enhanced Uptake"

  • Patent Identification: U.S. Patent No. 8,147,866, "Transmucosal Delivery Devices with Enhanced Uptake", issued April 3, 2012.

The Invention Explained

  • Problem Addressed: The patent seeks to overcome challenges in transmucosal drug delivery, where factors like saliva pH and secretion rate can lead to inconsistent drug absorption ('866 Patent, col. 2:35-44). The goal is to create a more predictable and efficient delivery system.
  • The Patented Solution: The invention is a bioerodable, multi-layered device for oral mucosal drug delivery. It consists of a "mucoadhesive polymeric diffusion environment" containing the drug (buprenorphine) and a "barrier environment" (backing layer) ('866 Patent, Abstract). This structure is designed to create a "unidirectional gradient," forcing the drug to flow primarily toward the absorptive mucosal tissue and minimizing the amount washed away by saliva, thereby enhancing uptake ('866 Patent, col. 2:53-64; Fig. 4A-C). The mucoadhesive layer is buffered to a specific pH to optimize the drug's ability to move through the film and be absorbed by the body ('866 Patent, col. 3:37-41).
  • Technical Importance: This design aimed to improve the bioavailability of transmucosally delivered drugs, allowing for a therapeutic effect with a smaller amount of medication and reducing side effects associated with drug that is swallowed and subjected to first-pass metabolism ('866 Patent, col. 10:51-65).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims from 1-12, based on a notice letter from the Defendants (Compl. ¶47). The lead independent claims are Claim 1 (a method) and Claim 8 (a device).
    • Independent Claim 1 (Method of use):
      • Administering buprenorphine via a mucoadhesive bioerodable drug delivery device applied to an oral mucosal surface.
      • The device comprises a bioerodable mucoadhesive layer with buprenorphine in a polymeric diffusion environment that is a "buffered environment having a pH of between about 4 and about 6."
      • The device also comprises an adjacent polymeric barrier layer.
      • This structure provides a "unidirectional gradient" for "rapid and efficient delivery" of the buprenorphine across the buffered environment.
    • Independent Claim 8 (Device):
      • A mucoadhesive bioerodable drug delivery device for transmucosal administration of buprenorphine.
      • The device comprises a bioerodable mucoadhesive layer with buprenorphine in a polymeric diffusion environment that is a "buffered environment having a pH between about 4 and about 6."
      • The device also comprises an adjacent polymeric barrier layer to provide a "unidirectional gradient."

U.S. Patent No. 9,655,843 - "Transmucosal Delivery Devices with Enhanced Uptake"

  • Patent Identification: U.S. Patent No. 9,655,843, "Transmucosal Delivery Devices with Enhanced Uptake", issued May 23, 2017.

The Invention Explained

  • Problem Addressed: As with the related '866 patent, this patent addresses the need for transmucosal devices that provide enhanced and more reliable uptake of a medicament ('843 Patent, col. 1:42-53).
  • The Patented Solution: The invention is a biodegradable drug delivery device with a layered structure to facilitate unidirectional drug flow to the buccal surface. It comprises a "bioerodible mucoadhesive layer" containing buprenorphine within a "polymeric diffusion environment" and an adjacent "polymeric barrier environment" ('843 Patent, Claim 1). A key distinction from the '866 patent is that the asserted claims of the '843 patent recite a broader pH range for the drug-containing layer.
  • Technical Importance: The technology provides a platform for efficient oral transmucosal delivery of drugs like buprenorphine, aiming for rapid onset and improved bioavailability compared to conventional oral dosage forms ('843 Patent, col. 2:48-56).

Key Claims at a Glance

  • The complaint alleges infringement of one or more claims from 1-25 (Compl. ¶61). The lead independent claims are Claim 1 (method of delivery), Claim 13 (a device), and Claim 25 (method of treating pain).
    • Independent Claim 1 (Method of delivery):
      • A method for delivering buprenorphine to a human by administering a mucoadhesive biodegradable drug delivery device.
      • The device comprises a bioerodible mucoadhesive layer with buprenorphine in a polymeric diffusion environment having a pH "between about 4 and about 7.5."
      • The device includes an adjacent polymeric barrier environment providing a "unidirectional diffusion gradient."
    • Independent Claim 13 (Device):
      • A device for delivering buprenorphine to a human comprising a bioerodible mucoadhesive layer with buprenorphine in a polymeric diffusion environment having a pH "between about 4 and about 7.5," and an adjacent polymeric barrier environment creating a unidirectional gradient.
    • Independent Claim 25 (Method of treating pain):
      • A method for treating pain by adhering a device to a human's buccal surface, where the device has a mucoadhesive layer with a therapeutic amount of buprenorphine in a polymeric diffusion environment "buffered to between about 4 and about 7.5" and an adjacent barrier layer.

U.S. Patent No. 9,901,539 - "Transmucosal Drug Delivery Devices for Use in Chronic Pain Relief"

  • Patent Identification: U.S. Patent No. 9,901,539, "Transmucosal Drug Delivery Devices for Use in Chronic Pain Relief", issued February 27, 2018.

Technology Synopsis

This patent is directed to methods for treating chronic pain by administering specific low doses of buprenorphine twice daily using a transmucosal drug delivery device ('539 Patent, Abstract). The invention claims a method of treatment that results in a specific steady-state plasma concentration of the drug, providing effective pain management while aiming to minimize common opioid-related side effects like constipation ('539 Patent, col. 2:11-18; Claim 1).

Asserted Claims

The complaint indicates claims 1-22 are at issue (Compl. ¶75). The lead independent claims are Claim 1 and Claim 9 (methods of treatment).

Accused Features

The complaint alleges that Defendants' filing of an ANDA for 600 mcg and 750 mcg buprenorphine buccal films, if approved, would induce infringement by physicians and patients who would use the generic product to practice the patented methods of treating chronic pain (Compl. ¶¶77, 79).

III. The Accused Instrumentality

Product Identification

  • The accused product is the "generic buprenorphine buccal film (600 mcg and 750 mcg)" for which Defendants seek FDA approval via the amended Abbreviated New Drug Application (ANDA) No. 212036 (Compl. ¶46).

Functionality and Market Context

  • The product is a generic version of the branded drug Belbuca®, a film designed for transmucosal (buccal) delivery of the opioid analgesic buprenorphine for pain management (Compl. ¶¶ 1, 44). As an ANDA product, it is intended to be bioequivalent to the branded drug. The complaint alleges that upon FDA approval, Defendants intend to "market, distribute, sell, and derive revenue from" the generic product in the United States, including in Delaware (Compl. ¶38). The complaint does not provide further technical details regarding the specific formulation or structure of the accused generic film.
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide narrative allegations or claim charts mapping specific features of the Defendants’ proposed generic product to the elements of the asserted claims. The infringement theory is predicated on the act of filing the amended ANDA No. 212036. Plaintiffs allege that the commercial manufacture, use, or sale of the generic buprenorphine buccal film described in the ANDA would directly infringe one or more claims of the patents-in-suit, either literally or under the doctrine of equivalents (Compl. ¶¶ 49, 63).

  • Identified Points of Contention:
    • Evidentiary Question: As validity is not at issue due to the stipulation in the related case, a central question will be evidentiary. The dispute will likely focus on what discovery into the confidential ANDA submission reveals about the precise formulation, pH, and layered structure of the Defendants' proposed film. The key question is whether this evidence will demonstrate the presence of the specific structural and compositional limitations of the asserted claims.
    • Technical Question: A core technical question will be one of functional and structural correspondence. Does the accused generic product contain distinct layers that function as the claimed "mucoadhesive polymeric diffusion environment" and "barrier environment" to create the required "unidirectional gradient," or can Defendants establish that their film has a materially different design or mechanism of action?
    • Scope Question: The infringement analysis will likely turn on the pH of the accused product. A key question is whether the pH of the Defendants' film falls within the scope of "between about 4 and about 6" as required by the '866 patent, or the broader "between about 4 and about 7.5" range recited in the '843 patent.

V. Key Claim Terms for Construction

  • The Term: "polymeric diffusion environment"

    • Context and Importance: This term defines the core drug-containing layer of the claimed invention. Its construction is critical because it will determine the scope of polymer compositions and structures covered by the claims. Practitioners may focus on this term because the dispute could center on whether the specific formulation of Defendants' generic film meets this definition.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification provides a non-exhaustive list of suitable polymers, including polyacrylic acid and various cellulosic polymers, which could support a reading that covers a wide range of mucoadhesive formulations ('866 Patent, col. 14:8-14).
      • Evidence for a Narrower Interpretation: The patent's detailed examples describe specific combinations of polymers ('866 Patent, col. 19:49-62). A party could argue that the term should be understood in light of these specific working embodiments, potentially limiting its scope.

  • The Term: "barrier environment"

    • Context and Importance: This term is essential to the "unidirectional gradient" limitation, which is a core concept of the invention. The infringement analysis depends on whether the accused film has a distinct structure that performs the claimed barrier function.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification defines the term functionally as an environment "capable of slowing or stopping flux of a medicament in its direction" ('866 Patent, col. 6:25-28). This language may support an interpretation covering any layer that achieves this result, regardless of its specific composition.
      • Evidence for a Narrower Interpretation: The patent's figures and descriptions of embodiments depict the barrier as a distinct backing layer that is "disposed adjacent to and coterminous with the mucoadhesive layer" ('866 Patent, col. 4:1-3; Fig. 4A). This could support a narrower construction requiring a discrete, co-extensive layer, rather than an integrated or partially-covering structure.

  • The Term: "buffered environment having a pH of between about 4 and about 6" ('866 Patent, Claim 1)

    • Context and Importance: This pH range is a key distinguishing limitation of the '866 patent claims. Given that the related '843 patent claims a different range (up to 7.5), the precise boundaries of this term, including the word "about," will be critical to the infringement analysis.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: A party might argue that "about" should be interpreted broadly to encompass values that achieve a similar result, pointing to the patent's overall goal of optimizing drug delivery rather than hitting a precise numerical target ('866 Patent, col. 2:35-44).
      • Evidence for a Narrower Interpretation: A party could argue the inventors acted as their own lexicographers by claiming different pH ranges in related patents, suggesting the "about 4 and about 6" range was intentionally chosen to be distinct and narrow. The specification's discussion of testing devices at pH 6.0, 7.25, and 8.5 could be used to argue the inventors understood these ranges to be meaningfully different ('866 Patent, col. 21:8-11).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement theory is based on allegations that Defendants have knowledge of the patents and intend for physicians and patients to infringe by prescribing and using the generic product in accordance with its label (Compl. ¶¶ 51, 65, 79). The contributory infringement theory alleges the generic film is a material part of the claimed methods and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶ 52, 66, 80).
  • Willful Infringement: The complaint alleges that Defendants' infringement is willful, asserting that they "acted without a reasonable basis for believing that they would not be liable" (Compl. ¶¶ 55, 69, 83). This allegation is based on Defendants' knowledge of the patents, which are listed in the FDA's Orange Book, and their participation in prior litigation concerning the same ANDA.

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

With patent validity seemingly off the table due to a prior stipulation, this ANDA case presents several focused questions for the court.

  • A central issue will be one of evidentiary proof: What will discovery into the confidential ANDA filing reveal about the precise formulation, pH, and physical structure of the Defendants' proposed generic film, and will that evidence be sufficient for Plaintiffs to show, by a preponderance of the evidence, that the product meets every limitation of the asserted claims?
  • A key legal question will be one of claim scope, particularly the construction of the pH limitations. The case may turn on whether the accused product's pH falls within the "between about 4 and about 6" range of the '866 patent or the broader "between about 4 and about 7.5" range of the '843 patent, and how the court interprets the scope of "about" in this context.
  • Finally, a determinative technical question will be one of structural equivalence: Does the accused product incorporate distinct layers that correspond to the claimed "mucoadhesive" and "barrier" environments to create a "unidirectional gradient," or can Defendants demonstrate that their film utilizes a fundamentally different, non-infringing design?