1:24-cv-00562
Neurelis Inc v. Padagis LLC
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Neurelis, Inc. (Delaware)
- Defendant: Padagis LLC (Delaware), Padagis US LLC (Delaware), and Padagis Israel Pharmaceuticals Ltd. (Israel)
- Plaintiff’s Counsel: DLA PIPER LLP (US)
- Case Identification: 1:24-cv-00562, D. Del., 05/08/2024
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendants Padagis LLC and Padagis US LLC are Delaware limited liability companies subject to personal jurisdiction in the district, and Defendant Padagis Israel is a non-resident defendant.
- Core Dispute: Plaintiff alleges that Defendants’ submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of VALTOCO® (diazepam nasal spray) infringes three patents related to pharmaceutical compositions for benzodiazepines.
- Technical Context: The technology concerns non-aqueous pharmaceutical formulations designed for the rapid nasal administration of benzodiazepines, a class of drugs used for the acute treatment of seizure clusters in epilepsy patients.
- Key Procedural History: This patent infringement action was initiated under the Hatch-Waxman Act following Defendants’ notification to Plaintiff, via a letter dated March 26, 2024, of their submission of ANDA No. 219320. This ANDA includes a “Paragraph IV Certification” alleging that Plaintiff’s patents are invalid, not enforceable, and/or not infringed. The complaint was filed within the 45-day statutory window, triggering a 30-month stay on FDA approval for the generic product. The asserted patents are listed in the FDA’s “Orange Book” as covering the branded drug VALTOCO.
Case Timeline
| Date | Event |
|---|---|
| 2008-03-28 | Priority Date for ’414 and ’786 Patents |
| 2011-12-13 | Priority Date for ’546 Patent |
| 2014-11-25 | Issue Date for U.S. Patent No. 8,895,546 |
| 2022-02-08 | Issue Date for U.S. Patent No. 11,241,414 |
| 2023-10-24 | Issue Date for U.S. Patent No. 11,793,786 |
| 2024-03-26 | Padagis ANDA Notice Letter Sent to Neurelis |
| 2024-05-08 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 8,895,546 - “Administration of Benzodiazepine Compositions”
The Invention Explained
- Problem Addressed: The patent family addresses the challenge of administering benzodiazepine drugs, which are poorly soluble in water, for acute conditions like seizures. Oral administration is too slow for an emergency, while intravenous administration is impractical outside of a clinical setting and rectal administration can be inconvenient (’414 Patent, col. 1:49-2:9; col. 17:62-66).
- The Patented Solution: The invention is a non-aqueous pharmaceutical solution for nasal administration that uses a carrier system to effectively dissolve the benzodiazepine drug. This carrier system combines tocopherols (a form of Vitamin E) with specific alcohols (ethanol and benzyl alcohol) to create a solvent for the drug, and includes an alkyl glycoside to enhance absorption through the nasal mucosa (’546 Patent, Abstract; col. 2:11-20).
- Technical Importance: This formulation provides a method for rapid, non-invasive, and convenient administration of a rescue medication for seizures, enabling caregivers or patients to treat acute seizure episodes effectively outside of a hospital (Compl. ¶20).
Key Claims at a Glance
- The complaint asserts infringement of claims 1-22, with a focus on independent claim 1 (Compl. ¶¶34-35).
- Essential elements of independent claim 1:
- A pharmaceutical solution for nasal administration consisting of:
- (a) a benzodiazepine drug;
- (b) one or more natural or synthetic tocopherols or tocotrienols... in an amount from about 30% to about 95% (w/w);
- (c) ethanol and benzyl alcohol in a combined amount from about 10% to about 70% (w/w); and
- (d) an alkyl glycoside.
U.S. Patent No. 11,241,414 - “Administration of Benzodiazepine Compositions”
The Invention Explained
- Problem Addressed: Similar to the ’546 patent, this patent addresses the need for a stable, rapidly absorbed, and non-invasively administered formulation for benzodiazepines to treat acute seizures (’414 Patent, col. 1:49-2:9).
- The Patented Solution: The ’414 patent claims a similar pharmaceutical solution but with greater specificity. The solution consists of diazepam as the benzodiazepine drug, a carrier system of tocopherols and a combination of ethanol and benzyl alcohol, and specifically identifies n-dodecyl beta-D-maltoside as the alkyl glycoside for enhancing nasal absorption (’414 Patent, Abstract; col. 6:53-61).
- Technical Importance: By specifying particular components like diazepam and n-dodecyl beta-D-maltoside, the invention provides a defined formulation for a widely used anti-seizure medication suitable for rapid nasal rescue therapy (Compl. ¶20).
Key Claims at a Glance
- The complaint asserts infringement of claims 1-3, 5-13, and 15-18, with a focus on independent claim 1 (Compl. ¶¶42-43).
- Essential elements of independent claim 1:
- A pharmaceutical solution for nasal administration consisting of:
- diazepam or a pharmaceutically acceptable salt thereof;
- one or more natural or synthetic tocopherols or tocotrienols... in an amount from 30% to 95% (w/w);
- ethanol and benzyl alcohol in a combined amount from 10% to 70% (w/w); and
- n-dodecyl beta-D-maltoside.
U.S. Patent No. 11,793,786 - “Administration of Benzodiazepine Compositions”
Technology Synopsis
This patent claims a pharmaceutical solution for nasal delivery of diazepam. The invention solves the problem of benzodiazepine solubility and delivery by using a formulation consisting of diazepam, a specific group of tocopherols or tocotrienols, one or more alcohols including benzyl alcohol, and n-dodecyl beta-D-maltoside (’786 Patent, Claim 1; Compl. ¶26).
Asserted Claims
Claims 1-3, 5-9, 11-13, and 15-27 are asserted, with independent claim 1 exemplified in the complaint (Compl. ¶¶51-52).
Accused Features
The complaint alleges that the formulation of Padagis’s generic diazepam nasal spray, as described in its ANDA, infringes the claims of the ’786 patent (Compl. ¶53).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is the “Padagis ANDA Product,” which is a generic version of VALTOCO® (diazepam nasal spray), 10 mg/spray, for which Padagis submitted ANDA No. 219320 to the FDA (Compl. ¶1).
Functionality and Market Context
The product is a prescription nasal spray intended as a rescue medicine for the short-term treatment of seizure clusters in epilepsy patients aged six and older (Compl. ¶20). As an ANDA product, it is intended to be a bioequivalent and lower-cost generic alternative to Neurelis's branded VALTOCO® product upon receiving FDA approval (Compl. ¶1, ¶29). The complaint alleges that the formulation of the Padagis ANDA Product contains the specific combination of ingredients claimed in the asserted patents (Compl. ¶¶36, 44, 53).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
The complaint does not provide a detailed claim chart or reference any claim chart exhibits. The infringement allegations are based on information from the Padagis Notice Letter, which allegedly details the composition of the Padagis ANDA Product (Compl. ¶¶36, 44, 53).
8,895,546 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical solution for nasal administration consisting of: | The Padagis ANDA Product is a pharmaceutical solution for nasal administration. | ¶1, ¶36 | col. 2:11-12 |
| (a) a benzodiazepine drug; | The Padagis ANDA Product contains the benzodiazepine drug diazepam. | ¶1, ¶36 | col. 15:35-42 |
| (b) one or more natural or synthetic tocopherols or tocotrienols... in an amount from about 30% to about 95% (w/w); | The Padagis ANDA Product is alleged to contain one or more tocopherols or tocotrienols in the claimed weight percentage range. | ¶36 | col. 2:13-17 |
| (c) ethanol and benzyl alcohol in a combined amount from about 10% to about 70% (w/w); and | The Padagis ANDA Product is alleged to contain ethanol and benzyl alcohol in the claimed combined weight percentage range. | ¶36 | col. 2:17-19 |
| (d) an alkyl glycoside. | The Padagis ANDA Product is alleged to contain an alkyl glycoside. | ¶36 | col. 13:25-60 |
11,241,414 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A pharmaceutical solution for nasal administration consisting of: | The Padagis ANDA Product is a pharmaceutical solution for nasal administration. | ¶1, ¶44 | col. 6:44-45 |
| diazepam or a pharmaceutically acceptable salt thereof; | The Padagis ANDA Product contains diazepam. | ¶1, ¶44 | col. 6:46-47 |
| one or more natural or synthetic tocopherols or tocotrienols... in an amount from 30% to 95% (w/w); | The Padagis ANDA Product is alleged to contain tocopherols or tocotrienols in the claimed weight percentage range. | ¶44 | col. 6:48-52 |
| ethanol and benzyl alcohol in a combined amount from 10% to 70% (w/w); and | The Padagis ANDA Product is alleged to contain ethanol and benzyl alcohol in the claimed combined weight percentage range. | ¶44 | col. 6:53-55 |
| n-dodecyl beta-D-maltoside. | The Padagis ANDA Product is alleged to contain n-dodecyl beta-D-maltoside. | ¶44 | col. 13:45-48 |
Identified Points of Contention
- Scope Questions: A central dispute may arise over the interpretation of the transitional phrase "consisting of." This term is highly restrictive in patent law. The question will be whether the Padagis ANDA product contains any unlisted components that are not mere impurities or processing aids, which could potentially place the formulation outside the literal scope of the claims. Further, the scope of the term "about," used to qualify the weight percentages of the components, will be a likely point of contention if the accused formulation's percentages are near the claimed boundaries.
- Technical Questions: As this is a notice-pleading complaint, the specific formulation of the Padagis ANDA Product is not detailed. A primary technical question for discovery will be to confirm the exact identity and weight percentages of all ingredients in the accused product and compare them to the claim limitations.
V. Key Claim Terms for Construction
The Term: "consisting of"
Context and Importance
This transitional phrase appears at the preamble of the asserted independent claims of all three patents (e.g., ’546 Patent, col. 18:13-14). Its construction is critical because it generally closes the claim to any elements not recited. If the Padagis ANDA Product contains additional, unlisted excipients that materially alter the formulation's characteristics, a court may find no literal infringement. Practitioners may focus on this term because the outcome of an infringement analysis in a chemical composition case often depends on whether unlisted ingredients are permissible.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The complaint does not provide sufficient detail for analysis of this element.
- Evidence for a Narrower Interpretation: The claims of the asserted patents consistently use "consisting of," a term of art indicating a strong presumption that the claim is closed to unrecited elements. The patentee’s choice to use this restrictive term, rather than the more open "comprising," suggests an intentional exclusion of other components from the core claimed solution.
The Term: "about"
Context and Importance
This term modifies the weight percentage ranges for the tocopherol and alcohol components in the asserted independent claims (e.g., ’546 Patent, col. 18:18-24). The definition of "about" will determine the effective boundaries of these ranges. If the Padagis product formulation lies close to, but not exactly within, the recited numerical limits, the interpretation of this term could be dispositive of infringement.
Intrinsic Evidence for Interpretation
- Evidence for a Broader Interpretation: The specification of the related ’414 patent uses the term in a way that may suggest flexibility, stating for example that the amount of alcohols can be "about 10% to about 55%, about 10% to about 40%, about 10% to about 35%" and numerous other overlapping ranges, which may imply that the precise endpoints are not critical to the invention's function (’414 Patent, col. 7:46-54).
- Evidence for a Narrower Interpretation: The patents provide specific formulations and stability data that may be tied to the recited ranges (e.g., ’414 Patent, Tables 3-1, 4-1). A party could argue that these examples define the practical and intended scope of "about," limiting it to a narrow degree of variance that maintains the disclosed stability and performance characteristics.
VI. Other Allegations
Indirect Infringement
The complaint alleges that upon FDA approval, Padagis will actively induce infringement under 35 U.S.C. § 271(b) and contribute to infringement under § 271(c) (Compl. ¶¶37, 45, 54). The alleged basis for inducement is that Padagis will manufacture, market, and sell the ANDA product with instructions that will inevitably lead end-users (patients and physicians) to administer the nasal spray in an infringing manner.
Willful Infringement
The complaint alleges that Padagis has acted with "full knowledge" of the asserted patents and without a reasonable basis for believing it would not be liable for infringement (Compl. ¶¶38, 47, 55). This allegation is based on Padagis’s pre-suit knowledge, evidenced by its submission of the Paragraph IV certification and the associated notice letter sent to Neurelis on March 26, 2024 (Compl. ¶29).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: can the highly restrictive claim term "consisting of" be interpreted to read on the Padagis ANDA formulation if discovery reveals the presence of any unlisted excipients, or will those excipients place the product outside the claims' literal scope?
- A second central question will be one of factual infringement: does the precise chemical composition of the Padagis ANDA product, particularly the weight percentages of its components, fall within the boundaries of the asserted claims, a determination that will likely depend on the judicial construction of the term "about"?
- A third key issue, raised by the defendant's Paragraph IV certification, will be one of patent validity: can Padagis prove by clear and convincing evidence that the asserted claims, which cover specific formulations of known components, are invalid as obvious over prior art methods of formulating benzodiazepines for nasal delivery?