DCT

1:19-cv-00444

BioDelivery Sciences Intl Inc v. Chemo

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:19-cv-00444, D. Del., 03/01/2019
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Delaware based on statutory grounds for patent cases. Jurisdiction is asserted over the various domestic and foreign defendants based on conduct including incorporation in Delaware (IntelGenx Tech), sales and distribution of products in Delaware, deriving substantial revenue from the state, and having previously availed themselves of the forum by participating in other patent litigation in the district.
  • Core Dispute: Plaintiff alleges that Defendants’ filing of an Abbreviated New Drug Application (ANDA) for a generic buprenorphine buccal film constitutes an act of infringement of three patents covering transmucosal drug delivery technology.
  • Technical Context: The technology concerns a bioerodable film for delivering opioid-based pain medication, such as buprenorphine, through the mucosal lining of the cheek, a method intended to enhance drug absorption and bioavailability.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 212036 to the FDA. The ANDA included a Paragraph IV certification, asserting that Plaintiffs’ patents listed in the FDA's Orange Book for the drug Belbuca® are invalid or would not be infringed by Defendants’ proposed generic product. Plaintiffs received a notice letter regarding the ANDA filing on January 31, 2019, and filed this complaint within the statutory 45-day window, triggering a potential 30-month stay on FDA approval of the generic product.

Case Timeline

Date Event
2006-07-21 Earliest Priority Date for ’866 and ’843 Patents
2011-12-21 Earliest Priority Date for ’539 Patent
2012-04-03 U.S. Patent No. 8,147,866 Issued
2015-10-23 Plaintiff's NDA for Belbuca® Approved
2017-05-23 U.S. Patent No. 9,655,843 Issued
2018-02-27 U.S. Patent No. 9,901,539 Issued
2019-01-31 Defendants Send Paragraph IV Notice Letter to Plaintiffs
2019-03-01 Complaint Filed

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

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

  • Issued: April 3, 2012 (Compl. ¶32)

The Invention Explained

  • Problem Addressed: The patent's background describes the challenge of achieving controlled and efficient absorption of a drug through the oral mucosa, noting that factors like saliva pH can negatively influence uptake ('866 Patent, col. 1:35-44).
  • The Patented Solution: The invention is a bioerodable, layered film designed to adhere to the mucosal surface (e.g., the inside of the cheek). It consists of a "mucoadhesive polymeric diffusion environment" containing the drug and a "barrier environment" or backing layer. This two-part structure is designed to create a "unidirectional gradient" that directs the drug toward the absorptive tissue of the mucosa while preventing it from being washed away by saliva. The pH of the mucoadhesive layer is also buffered to a specific range to optimize drug absorption ('866 Patent, col. 2:53-65).
  • Technical Importance: This design aims to provide a more efficient and predictable delivery mechanism for transmucosal drugs, which can lead to higher bioavailability and a more rapid onset of therapeutic effect compared to drugs that must pass through the gastrointestinal system ('866 Patent, col. 7:10-20).

Key Claims at a Glance

  • The complaint alleges infringement of one or more of claims 1-12 (Compl. ¶36, 37). The lead independent claims are 1 (a method of delivery) and 8 (a device).
  • Independent Claim 1 (Method): The essential elements include (1) administering buprenorphine via a mucoadhesive bioerodable device on an oral mucosal surface, where the device comprises (2) a bioerodable mucoadhesive layer with buprenorphine in a polymeric diffusion environment buffered to a pH between about 4 and 6, and (3) an adjacent barrier layer that creates a unidirectional gradient to deliver the drug across the environment to the mucosa ('866 Patent, col. 27:1-12).
  • Independent Claim 8 (Device): The essential elements describe (1) a mucoadhesive bioerodable device for transmucosal buprenorphine administration, comprising (2) a mucoadhesive layer with buprenorphine in a buffered polymeric environment (pH between about 4 and 6), and (3) an adjacent barrier layer creating a unidirectional gradient for rapid and efficient delivery ('866 Patent, col. 27:26-28:22).

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

  • Issued: May 23, 2017 (Compl. ¶46)

The Invention Explained

  • Problem Addressed: Like the parent '866 patent, this invention seeks to overcome challenges in transmucosal drug delivery to ensure more reliable and efficient drug uptake ('843 Patent, col. 1:30-48).
  • The Patented Solution: The patent describes the same core technology of a layered, mucoadhesive film with a barrier layer to create a unidirectional flow of the active agent, buprenorphine, to the buccal mucosa. The claims in this patent recite a different, broader pH range for the polymeric diffusion environment than the '866 patent ('843 Patent, Abstract; col. 3:1-24).
  • Technical Importance: The invention provides an improved platform for pain management by enabling efficient delivery of buprenorphine, a potent analgesic, directly into the bloodstream while avoiding first-pass metabolism in the liver ('843 Patent, col. 9:1-14).

Key Claims at a Glance

  • The complaint alleges infringement of one or more of claims 1-25 (Compl. ¶50, 51). The lead independent claims are 1 (a method of delivery) and 13 (a device).
  • Independent Claim 1 (Method): The essential elements include (1) a method of delivering buprenorphine to a human by (2) administering a mucoadhesive biodegradable device to a buccal surface, the device comprising (3) a bioerodible mucoadhesive layer containing buprenorphine in a polymeric diffusion environment with a pH between about 4 and about 7.5, and (4) an adjacent polymeric barrier environment that creates a unidirectional diffusion gradient ('843 Patent, col. 27:10-24).
  • Independent Claim 13 (Device): The essential elements describe (1) a device for delivering buprenorphine to a human, comprising (2) a bioerodible mucoadhesive layer with buprenorphine in a polymeric diffusion environment with a pH between about 4 and about 7.5, and (3) an adjacent polymeric barrier environment, which together create a unidirectional diffusion gradient upon application to a buccal surface ('843 Patent, col. 27:50-28:10).

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

  • Issued: February 27, 2018 (Compl. ¶60)

Technology Synopsis

This patent claims methods of treating chronic pain in opioid-experienced subjects by administering specific low doses of buprenorphine using a mucoadhesive device. The invention aims to provide a steady-state plasma concentration of the drug that is sufficient for analgesia but minimizes common opioid-related side effects, such as constipation ('539 Patent, Abstract; col. 2:10-23).

Asserted Claims

The complaint alleges infringement of one or more of claims 1-22 (Compl. ¶64, 65). The independent claims are 1 and 9, both directed to methods of treatment.

Accused Features

The complaint alleges that Defendants’ filing of ANDA No. 212036 for a generic buprenorphine buccal film, which would be prescribed for the same or similar uses, constitutes an act of infringement of these method claims (Compl. ¶62, 65).

III. The Accused Instrumentality

Product Identification

Defendants’ generic "Buprenorphine Buccal Film" as detailed in Abbreviated New Drug Application (ANDA) No. 212036, for which Defendants seek FDA approval (Compl. ¶34, 48, 62).

Functionality and Market Context

The accused product is a generic version of Plaintiffs’ branded drug, Belbuca®, and is a film designed to deliver buprenorphine for pain management via the buccal (inner cheek) route (Compl. ¶1, 33). The ANDA seeks approval for commercial manufacture and sale in the United States in dosages of 75 mcg, 150 mcg, 300 mcg, 450 mcg, and 900 mcg (Compl. ¶34). As this case is brought under 35 U.S.C. § 271(e)(2), the act of infringement is the filing of the ANDA itself, which proposes a product that, if marketed, would allegedly infringe the patents-in-suit (Compl. ¶37). The product's commercial importance stems from its position as a potential generic competitor to Belbuca®, which is listed in the FDA's Orange Book (Compl. ¶33).

  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint, as is typical in ANDA litigation, does not provide a detailed claim chart or specific factual allegations mapping the accused product’s features to the patent claims. The infringement theory under 35 U.S.C. § 271(e)(2) is predicated on the act of filing the ANDA itself. Plaintiffs allege that the product described in ANDA No. 212036, if approved and marketed, would be bioequivalent to Plaintiffs’ Belbuca® product and would be made, used, and sold in a manner that directly infringes one or more claims of the patents-in-suit, literally or under the doctrine of equivalents (Compl. ¶37, 51, 65). The complaint further alleges that the proposed product label would instruct physicians and patients to use the film in a manner that infringes the asserted method claims (Compl. ¶39, 53, 67).

Identified Points of Contention

  • Scope Questions: A primary dispute will likely concern whether the specific formulation of Defendants' generic film falls outside the scope of the claims. For the ’866 Patent, a key question will be whether the accused product's mucoadhesive layer is buffered to a pH "between about 4 and about 6." For all patents, a central issue may be whether the film's structure creates a "unidirectional gradient" as the patents describe that term.
  • Technical Questions: A key evidentiary question will be whether the physical composition and performance of the accused generic film meet every limitation of the asserted claims. For example, what evidence exists within the ANDA filing that the accused product contains both a "mucoadhesive polymeric diffusion environment" and a distinct "barrier environment," as opposed to a different structure, such as a monolithic film with different diffusion properties?

V. Key Claim Terms for Construction

"buffered environment" ('866 Patent, cl. 1; '843 Patent, cl. 1)

Context and Importance

The patents teach that controlling the pH of the device is important for optimizing drug uptake. The definition of this term is critical because infringement may depend on whether the accused product's formulation is found to have the claimed buffering characteristics. Practitioners may focus on this term because Defendants could argue their formulation's pH is merely incidental and not the result of a "buffered environment."

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The specification discloses that the environment's properties "can be manipulated by, e.g., the pH" and lists various buffering agents as examples, which may support a construction covering any formulation that is intentionally designed to control pH upon administration ('866 Patent, col. 6:20-24; col. 12:20-30).
  • Evidence for a Narrower Interpretation: The specification lists specific buffering systems, such as phosphates and citrates. This could support an argument that the term is limited to formulations containing conventional buffering agents and does not extend to excipients that only incidentally affect pH ('866 Patent, col. 12:20-30).

"unidirectional gradient" ('866 Patent, cl. 1; '843 Patent, cl. 1)

Context and Importance

This term describes the core mechanism of action for the patented two-layer device. The infringement analysis will turn on whether the accused product is structured to force drug flux primarily toward the mucosa.

Intrinsic Evidence for Interpretation

  • Evidence for a Broader Interpretation: The patent defines the term as a gradient that "allows for the flux of a medicament... in substantially one direction" and notes that the barrier environment "slows or stops" flux in other directions, suggesting that absolute unidirectionality is not required ('866 Patent, col. 6:25-34). The figures also depict embodiments where the barrier does not fully enclose the mucoadhesive layer, which may support a broader reading ('866 Patent, Figs. 4B-4C).
  • Evidence for a Narrower Interpretation: The specification states that in some embodiments, "the barrier environment stops flux of a medicament, except in the direction of the mucosa" ('866 Patent, col. 6:28-29). This language could be used to argue for a stricter interpretation requiring a near-complete blockage of drug flow into the oral cavity.

VI. Other Allegations

Indirect Infringement

The complaint alleges both induced and contributory infringement. Inducement is based on the allegation that Defendants know of the patents and that their product's instructions and label will inevitably cause physicians and patients to perform the patented methods of use (Compl. ¶39, 53, 67). Contributory infringement is based on the allegation that the generic film is a material component of the patented methods and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶40, 54, 68).

Willful Infringement

Willfulness is alleged based on Defendants' knowledge of the patents, as evidenced by their Paragraph IV certification and notice letter. The complaint asserts that Defendants "acted without a reasonable basis for believing that they would not be liable" and that their positions on invalidity and non-infringement "are devoid of any objective good-faith basis" (Compl. ¶43-44, 57-58, 71-72).

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

  • A core issue will be one of claim construction and scope: can the term "unidirectional gradient," which is central to the patents' claimed mechanism, be interpreted to read on the specific physical structure and diffusion properties of the Defendants' generic film, or will Defendants be able to demonstrate a meaningful structural or functional difference?
  • A second key question will be definitional precision: the infringement analysis for the ’866 Patent will hinge on the court's construction of the pH range "between about 4 and about 6." Whether the accused product's pH falls within the boundary of "about" will be a critical and fact-intensive inquiry.
  • Finally, a determinative issue will be one of validity: separate from infringement, the case will depend on whether Defendants can prove by clear and convincing evidence that the asserted patent claims are invalid as anticipated or obvious in light of prior art, a position they asserted in their Paragraph IV certification.