DCT
1:25-cv-00010
Acacia Pharma Ltd v. Galenicum Health Slu
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Acacia Pharma Limited (United Kingdom), PAION UK Ltd (United Kingdom), and Eagle Pharmaceuticals, Inc. (Delaware)
- Defendant: Galenicum Health S.L.U. (Spain)
- Plaintiff’s Counsel: McCarter & English, LLP
- Case Identification: 1:25-cv-00010, D. Del., 01/03/2025
- Venue Allegations: Venue is alleged to be proper because the Defendant is a foreign corporation that may be sued in any judicial district.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) seeking to market a generic version of the sedative BYFAVO® (remimazolam) constitutes an act of infringement of two patents covering specific fixed-dosing regimens for the drug.
- Technical Context: The technology relates to pharmaceutical dosing methods for procedural sedatives, specifically for remimazolam, an ultra-short-acting benzodiazepine used to sedate patients for minor medical procedures.
- Key Procedural History: The lawsuit was filed under the Hatch-Waxman Act following Plaintiffs' receipt of a Notice Letter from the Defendant. This letter contained a Paragraph IV certification asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by the proposed generic product. The asserted patents are listed in the FDA's "Orange Book" for the branded drug BYFAVO®.
Case Timeline
| Date | Event |
|---|---|
| 2010-11-08 | Priority Date for ’236 and ’251 Patents |
| 2017-02-07 | U.S. Patent No. 9,561,236 Issued |
| 2017-11-28 | U.S. Patent No. 9,827,251 Issued |
| 2020-07-02 | FDA Approval of BYFAVO® NDA |
| 2024-11-21 | Plaintiffs' Receipt of Defendant's ANDA Notice Letter |
| 2025-01-03 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 9,561,236 - "Dosing Regimen for Sedation with CNS 7056 (Remimazolam)", issued February 7, 2017
The Invention Explained
- Problem Addressed: The patent describes the challenge of establishing an optimal dosing regimen for sedatives, which exhibit high inter-individual variability in patient response. Specifically for the sedative remimazolam (CNS 7056), traditional body-weight adjusted dosing, especially when combined with the opioid fentanyl, led to deficiencies including procedural failures, "dropouts" (patients who never achieve adequate sedation), and adverse events like hypotension (’236 Patent, col. 1:41-55; col. 2:31-56).
- The Patented Solution: The patent proposes abandoning weight-based dosing in favor of a fixed-dose regimen. The invention is a method of sedating a subject by administering an initial fixed dose of remimazolam besylate between 2 mg and 10 mg, irrespective of the patient's body weight, in combination with an opioid (’236 Patent, Abstract). The specification explains that extensive pharmacokinetic and pharmacodynamic analysis revealed that body weight was not a statistically significant predictor of the drug's clearance, making a fixed-dose approach a safer and more effective alternative (’236 Patent, col. 8:3-9).
- Technical Importance: This fixed-dose approach represented a move away from the conventional wisdom of titrating sedatives based on patient weight, aiming to simplify administration and reduce the risk of under- or over-sedation.
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (’236 Patent, col. 41:29-42; Compl. ¶33-34).
- The essential elements of Claim 1 are:
- A method of sedating a subject
- comprising administering to the subject an initial dose of the besylate salt of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester (CNS 7056) of formula (I)
- wherein the initial dose is a fixed dose of between about 2 mg and about 10 mg
- and is irrespective of the body weight of the subject,
- in combination with one or more doses of an opioid.
U.S. Patent No. 9,827,251 - "Dosing Regimen for Sedation with CNS 7056 (Remimazolam)", issued November 28, 2017
The Invention Explained
- Problem Addressed: As a continuation of the application leading to the ’236 Patent, this patent addresses the same technical problem: the high variability and potential for adverse events associated with conventional weight-based dosing of the sedative remimazolam (’251 Patent, col. 1:41-55; col. 2:31-56).
- The Patented Solution: The invention claims a method of sedation by administering one or more fixed doses of remimazolam besylate, wherein the administered amount does not depend on the subject's body weight (’251 Patent, Abstract). This method covers the administration of fixed doses for sedation generally, not limited to just the initial dose or co-administration with an opioid as in the lead claim of the '236 Patent (’251 Patent, col. 40:15-29).
- Technical Importance: This patent broadens the fixed-dosing concept to cover sedation methods where the dosage amount is determined without reference to patient body weight, seeking to improve safety and predictability.
Key Claims at a Glance
- The complaint asserts infringement of at least independent claim 1 (’251 Patent, col. 40:15-29; Compl. ¶48-49).
- The essential elements of Claim 1 are:
- A method of sedating a subject undergoing a procedure,
- comprising administering intravenously to the subject one or more fixed doses of a composition comprising the besylate salt of 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepin-4-yl]-propionic methyl ester (CNS 7056) of formula (I),
- wherein the amount of the besylate salt of the compound of formula (I) administered to the subject does not depend on the body weight of the subject.
III. The Accused Instrumentality
Product Identification
- The accused instrumentality is "Galenicum's Proposed ANDA Product," a generic version of BYFAVO® (remimazolam) (Compl. ¶1).
Functionality and Market Context
- The product is described as a white to off-white lyophilized powder for intravenous injection, containing 20 mg of remimazolam per vial, which is reconstituted to a final concentration of 2.5 mg/mL (Compl. ¶29). Its purpose is for the induction and maintenance of procedural sedation in adults for procedures lasting 30 minutes or less (Compl. ¶2).
- The complaint alleges that the proposed product is a direct generic competitor to the Plaintiffs' branded BYFAVO® product (Compl. ¶2). The core of the infringement allegation is not the product itself, but the instructions for its use that will be included in its FDA-approved labeling, which Plaintiffs allege will direct medical professionals to use the product in an infringing manner (Compl. ¶31, 35, 50). The complaint includes a chemical structure diagram of the active ingredient remimazolam, which is identical in the patents and the accused product (Compl. ¶33, 48).
IV. Analysis of Infringement Allegations
- ’236 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of sedating a subject comprising administering to the subject an initial dose of the besylate salt of...formula (I) | The proposed product label will instruct healthcare providers to administer an initial dose of Galenicum's product, which contains the besylate salt of remimazolam as shown in formula (I). | ¶34, 33 | col. 41:29-35 |
| wherein the initial dose is a fixed dose of between about 2 mg and about 10 mg | The label will allegedly instruct administering an initial fixed dose that falls within the 2 mg to 10 mg range. | ¶34 | col. 41:35-37 |
| and is irrespective of the body weight of the subject, | The label's instructions for the initial dose will allegedly not be based on the patient's body weight. | ¶34 | col. 41:37-39 |
| in combination with one or more doses of an opioid. | The label will allegedly instruct for use of the product in combination with an opioid, such as fentanyl. | ¶34 | col. 41:40-42 |
- ’251 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| [a] method of sedating a subject undergoing a procedure, comprising administering intravenously to the subject one or more fixed doses of a composition comprising the besylate salt of...formula (I) | The proposed product label will instruct healthcare providers to intravenously administer one or more fixed doses of Galenicum's product, which contains the besylate salt of remimazolam as shown in formula (I). | ¶49, 48 | col. 40:15-25 |
| wherein the amount of the besylate salt of the compound of formula (I) administered to the subject does not depend on the body weight of the subject. | The dosing instructions in the proposed label will allegedly specify amounts that do not depend on patient body weight. | ¶49 | col. 40:26-29 |
- Identified Points of Contention:
- Factual Question: The central dispute will be factual: what will the final, FDA-approved label for Galenicum's product instruct? The case for induced infringement rests entirely on the content of a document (the proposed label) that is not yet part of the public record, with the complaint proceeding on "information and belief" (Compl. ¶34, 49).
- Scope Questions: A primary question for the court will be whether the dosing instructions on the proposed label meet every limitation of the asserted claims. For the ’236 Patent, this includes whether the specified dose is "between about 2 mg and about 10 mg" and whether its use "in combination with... an opioid" is mandated or merely suggested. For the ’251 Patent, the question is whether the label directs administration of "one or more fixed doses" in a manner that "does not depend on the body weight of the subject."
V. Key Claim Terms for Construction
The Term: "fixed dose" (’236 Patent, cl. 1; ’251 Patent, cl. 1)
- Context and Importance: This term is at the heart of the patented invention, distinguishing it from prior art weight-based dosing. Its construction is critical because the infringement analysis will depend on whether the dosing instructions in the accused label (which may provide a range or some physician discretion) fall within the scope of a "fixed dose."
- Intrinsic Evidence for a Broader Interpretation: The patent specification explicitly defines the term as "an amount of a drug given to a patient irrespective of his body weight" (’236 Patent, col. 4:61-64; ’251 Patent, col. 4:51-54). This definition could support an interpretation covering any non-weight-based dosing scheme.
- Intrinsic Evidence for a Narrower Interpretation: The detailed description provides specific dosing combinations, such as "8 mg initial dose plus 3 mg top-up dose" (’236 Patent, col. 7:8-9; ’251 Patent, col. 7:7-8). A party could argue these specific examples narrow the term to discrete, predetermined amounts rather than flexible ranges.
The Term: "in combination with" (’236 Patent, cl. 1)
- Context and Importance: This term defines the required relationship between the administration of remimazolam and an opioid. The infringement analysis for the ’236 patent will turn on whether the accused label instructs a temporal and functional relationship that satisfies this limitation.
- Intrinsic Evidence for a Broader Interpretation: The specification defines the phrase to mean that the two drugs are given "within a time frame, where both substances exhibit a pharmacological effect," which is preferably not longer than 10 minutes (’236 Patent, col. 4:46-53). This suggests a relatively broad window for co-administration.
- Intrinsic Evidence for a Narrower Interpretation: The patent's clinical study examples describe specific protocols where fentanyl was administered "5-10 minutes before CNS 7056" (’236 Patent, col. 15:7-8). A party may argue this context limits the claim to methods where the opioid is administered shortly before the sedative.
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement. The inducement theory is based on the allegation that Galenicum, upon receiving FDA approval, will sell its product with a label that provides instructions and encourages healthcare providers to administer the drug in a manner that directly infringes the asserted method claims (Compl. ¶43, 58). The contributory infringement theory alleges that the product is "especially made or adapted for use in infringing" the patents and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶44, 59).
- Willful Infringement: The complaint does not explicitly allege "willful" infringement. However, it alleges that Galenicum had knowledge of the asserted patents at least because they are listed in the FDA's Orange Book for the BYFAVO® drug product (Compl. ¶42, 57). The complaint requests a declaration that this is an "exceptional case" and an award of attorneys' fees pursuant to 35 U.S.C. § 285 (Compl. ¶61(e)).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of induced infringement: will the specific instructions on Galenicum's final, FDA-approved product label direct healthcare providers to administer generic remimazolam using a method that satisfies every limitation of the asserted claims? The outcome will depend on a factual comparison between the label's text and the claim language.
- A key legal question will be one of claim scope: can the term "fixed dose," defined in the patent as simply "irrespective of body weight," be construed to cover a dosing regimen that may be presented as a range or allow for physician discretion, or is its meaning limited by the specific dose amounts disclosed in the patent's examples?
- Given the defendant's Paragraph IV certification, a determinative issue for the court will be the validity of the asserted claims. The defense will likely argue that the claimed fixed-dosing regimen was obvious in light of prior art methods that relied on body-weight-based dosing and dose titration to achieve sedation.