DCT

1:25-cv-00382

UCB Inc v. Hikma Pharma USA Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00382, D. Del., 03/28/2025
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Hikma Pharmaceuticals USA Inc. is a Delaware corporation and Defendant Hikma Pharmaceuticals PLC is subject to personal jurisdiction in the district through its business contacts and litigation history.
  • Core Dispute: Plaintiffs allege that Defendant’s filing of an Abbreviated New Drug Application (ANDA) to market a generic version of NAYZILAM® (midazolam nasal spray) constitutes an act of infringement of four U.S. patents covering pharmaceutical compositions for nasal drug delivery.
  • Technical Context: The technology relates to liquid pharmaceutical formulations using specific polymers as solvents to enable the rapid, non-invasive nasal administration of poorly water-soluble drugs for treating acute medical conditions like epileptic seizures.
  • Key Procedural History: The litigation was initiated under the Hatch-Waxman Act following Defendant’s submission of ANDA No. 219736 with a Paragraph IV certification, seeking FDA approval to market its generic product prior to the expiration of the patents-in-suit. The complaint alleges that Defendant’s February 14, 2025 notice letter did not contest infringement of numerous asserted claims.

Case Timeline

Date Event
2007-01-19 Priority Date for ’033, ’322, ’432, and ’495 Patents
2012-07-10 U.S. Patent No. 8,217,033 Issues
2014-08-19 U.S. Patent No. 8,809,322 Issues
2016-03-22 U.S. Patent No. 9,289,432 Issues
2017-06-27 U.S. Patent No. 9,687,495 Issues
2019-05-17 FDA Approves NAYZILAM® New Drug Application
2025-02-14 Defendant Sends Paragraph IV Notice Letter to Plaintiffs
2025-03-28 Complaint for Patent Infringement Filed

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

U.S. Patent No. 8,217,033 - Methods and Compositions for the Delivery of a Therapeutic Agent

The Invention Explained

  • Problem Addressed: The patent’s background section describes the disadvantages of administering therapeutic agents by injection, such as the need for trained personnel, pain, and irritation, particularly for repeated doses. While mucosal administration (e.g., nasal) is an attractive alternative, its effectiveness is often limited by the poor water solubility of many drugs, which necessitates large, impractical volumes that can lead to inconsistent dosing and loss of the therapeutic agent. (’033 Patent, col. 1:21-col. 2:15).
  • The Patented Solution: The invention provides a liquid pharmaceutical composition that uses a specific class of solvents—alkoxy-polyethylene glycols (such as methoxy-polyethylene glycol, or mPEG)—to dissolve poorly soluble therapeutic agents. This allows for the creation of a concentrated formulation that can be delivered in a small, effective volume via the nasal mucosa. The specification explains that these formulations are less viscous and cause less irritation than compositions using other excipients, thereby improving spray characteristics and patient tolerance. (’033 Patent, Abstract; col. 3:28-54).
  • Technical Importance: This formulation technology enables rapid, non-invasive systemic drug delivery for acute conditions, potentially achieving therapeutic plasma concentrations nearly as fast as intravenous administration without the associated drawbacks. (’033 Patent, col. 2:20-36).

Key Claims at a Glance

  • The complaint asserts infringement of claims of the ’033 Patent, noting that Defendant did not contest infringement of claims 1-14 in its notice letter (Compl. ¶51-52). Independent claim 1 is representative.
  • Independent Claim 1:
    • A liquid pharmaceutical composition formulated for intranasal administration, comprising:
    • i) midazolam or a pharmaceutically salt thereof; and
    • ii) a methoxy-polyethylene glycol selected from the group consisting of methoxy-polyethylene glycol 350 and methoxy-polyethylene glycol 550.

U.S. Patent No. 8,809,322 - Methods and Compositions for the Delivery of a Therapeutic Agent

The Invention Explained

  • Problem Addressed: The ’322 Patent addresses the same technical problem as the ’033 Patent: the challenge of rapidly and non-invasively delivering poorly water-soluble drugs, which often requires injections or results in inefficient mucosal absorption from large-volume formulations. (’322 Patent, col. 1:21-col. 2:15).
  • The Patented Solution: The solution is also a liquid pharmaceutical composition utilizing a methoxy-polyethylene glycol solvent. The claims of the ’322 Patent define the methoxy-polyethylene glycol by its chemical formula and the average number of its repeating oxyethylene units, rather than by its average molecular weight as in the ’033 Patent. This approach also yields a low-viscosity, less irritating, and effective formulation for nasal delivery. (’322 Patent, Abstract; col. 3:28-54).
  • Technical Importance: As with the ’033 Patent, this technology provides a vehicle for rapid, non-invasive administration of drugs for acute conditions, offering a practical alternative to injection. (’322 Patent, col. 2:20-36).

Key Claims at a Glance

  • The complaint asserts infringement of claims of the ’322 Patent, noting that Defendant did not contest infringement of any claim in its notice letter (Compl. ¶61-62). Independent claim 1 is representative.
  • Independent Claim 1:
    • A liquid pharmaceutical composition formulated for intranasal administration comprising:
    • a) a therapeutically effective amount of a therapeutic agent selected from midazolam, a pharmaceutically acceptable salt thereof or combinations thereof; and
    • b) a methoxy-polyethylene glycol of Formula I: H₃C—O—(CH₂CH₂O)n—H
    • wherein n is a number in the range of 2 to 12.

U.S. Patent No. 9,289,432 - Methods and Compositions for the Delivery of a Therapeutic Agent

  • Patent Identification: U.S. Patent No. 9,289,432, issued March 22, 2016 (Compl. ¶36).
  • Technology Synopsis: This patent addresses the technical challenge of delivering poorly water-soluble drugs non-invasively. It discloses a liquid pharmaceutical composition containing a benzodiazepine (such as midazolam) and a methoxy-polyethylene glycol excipient, which creates a low-volume, low-viscosity formulation suitable for effective nasal administration. (’432 Patent, Abstract; col. 1:21-col. 2:15).
  • Asserted Claims: The complaint asserts infringement of claims of the ’432 Patent, noting that infringement of claims 1-14 was not contested by Defendant (Compl. ¶71-72). Independent claim 1 is asserted.
  • Accused Features: The accused feature is the entire formulation of Defendant’s generic Midazolam nasal spray as described in its ANDA filing (Compl. ¶70-71).

U.S. Patent No. 9,687,495 - Methods and Systems for the Delivery of a Therapeutic Agent

  • Patent Identification: U.S. Patent No. 9,687,495, issued June 27, 2017 (Compl. ¶37).
  • Technology Synopsis: This patent claims a system for nasal drug delivery. The system comprises a nasal spray device containing a liquid pharmaceutical composition that includes a benzodiazepine therapeutic agent and a methoxy-polyethylene glycol solvent, enabling effective nasal delivery in a small, administrable volume. (’495 Patent, Abstract; col. 1:21-col. 2:15).
  • Asserted Claims: The complaint asserts infringement of claims of the ’495 Patent, noting that infringement of claims 1-14 was not contested by Defendant (Compl. ¶81-82). Independent claim 1 is asserted.
  • Accused Features: The accused features are Defendant’s generic Midazolam nasal spray product in combination with the device intended for its administration (Compl. ¶80-81).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendant Hikma’s proposed generic Midazolam nasal spray (5mg), referred to as the "ANDA Product" (Compl. ¶1).
  • Functionality and Market Context: The complaint alleges that the ANDA Product, if approved, will have the same indication as Plaintiffs' branded product, NAYZILAM®. This indication is for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity in patients with epilepsy. (Compl. ¶31, ¶42). The ANDA Product is intended to be a generic version of NAYZILAM® and, upon FDA approval, is expected to be commercially manufactured, marketed, and sold in the United States, thereby displacing sales of the branded product (Compl. ¶1, ¶25).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint’s infringement theory is based on 35 U.S.C. § 271(e)(2)(A), where the act of submitting an ANDA to obtain approval for a generic drug before the expiration of patents covering that drug is a technical act of infringement. The complaint alleges that the ANDA Product is a generic version of NAYZILAM® and will have the same active ingredient, dosage form, and indication for use (Compl. ¶1, ¶42). Therefore, the complaint alleges that the composition of the ANDA Product will meet the limitations of the asserted claims.

’033 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
i) midazolam or a pharmaceutically salt thereof The ANDA Product is a Midazolam nasal spray (5mg), which contains the active ingredient midazolam. ¶1 col. 10:11-12
ii) a methoxy-polyethylene glycol selected from the group consisting of methoxy-polyethylene glycol 350 and methoxy-polyethylene glycol 550 The complaint alleges that the ANDA Product, as a generic version of NAYZILAM®, contains a formulation with this excipient. ¶1; ¶51 col. 6:55-60

’322 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
a) a therapeutically effective amount of a therapeutic agent selected from midazolam, a pharmaceutically acceptable salt thereof or combinations thereof The ANDA Product is a 5mg Midazolam nasal spray, which contains a therapeutically effective amount of midazolam. ¶1 col. 10:14-15
b) a methoxy-polyethylene glycol of Formula I ... wherein n is a number in the range of 2 to 12 The complaint alleges that the ANDA Product, as a generic version of NAYZILAM®, contains a formulation with an mPEG polymer having an average chain length within this range. ¶1; ¶61 col. 6:21-28
  • Identified Points of Contention:
    • Scope Questions: A central question for the court will be whether the specific excipients used in the Hikma ANDA Product fall within the scope of the claims. For instance, does the specific methoxy-polyethylene glycol used in the ANDA Product possess an average molecular weight that constitutes "methoxy-polyethylene glycol 350" as that term is used in the ’033 Patent, and an average number of repeating units that falls "in the range of 2 to 12" as required by the ’322 Patent?
    • Technical Questions: Because infringement for many claims was allegedly not contested, the dispute may focus on patent validity. However, based on the complaint alone, a key technical question is what evidence will be presented from the confidential ANDA submission to demonstrate that the proposed generic formulation literally meets every element of the asserted composition and system claims.

V. Key Claim Terms for Construction

  • The Term: "methoxy-polyethylene glycol 350" (’033 Patent, Claim 1)

  • Context and Importance: This term defines the primary excipient and is central to the invention. The precise scope of "350" will be critical, as a defendant could argue its formulation uses a polymer with a different average molecular weight that falls outside a proper construction of the term.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The specification defines "mPEG 350" as a "methoxy polyethylene glycol having an average molecular weight of about 350" (’033 Patent, col. 6:58-60, emphasis added). The use of "about" may support a construction that includes a range of molecular weights around 350.
    • Evidence for a Narrower Interpretation: The specification also refers to a specific commercial product, "Carbowax™ mPEG 350" (’033 Patent, col. 7:1-3). This could support an argument that the term should be construed more narrowly to cover only polymers with properties consistent with that specific commercial embodiment.

  • The Term: "n is a number in the range of 2 to 12" (’322 Patent, Claim 1)

  • Context and Importance: This limitation defines the length of the polymer chain for the key excipient. Infringement may turn on whether the polymer in the accused product has an average number of repeating units that falls strictly within this numerical range.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent states that "n, which is the average number of oxyethylene repeating units, is a number in the range of from about 1 to about 25" (’322 Patent, col. 5:1-3, emphasis added). Describing 'n' as an average suggests it represents a distribution, which may support construing the range to cover formulations where the average falls within 2 to 12, even if some individual polymer chains do not.
    • Evidence for a Narrower Interpretation: The patent discloses preferred sub-ranges, such as "from about 3 to about 10" (’322 Patent, col. 6:27-28). A party might argue that these specific ranges, combined with the lack of broadening language like "about" in claim 1 itself, suggest the boundaries "2" and "12" should be interpreted as absolute limits for the average value.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement against Hikma. The factual basis for this allegation is that, upon FDA approval, Hikma will "knowingly and intentionally include a product label and insert containing instructions for administering the ANDA Product," which will induce physicians, pharmacies, and end users to directly infringe the claims by using the product. (Compl. ¶55, ¶65, ¶75, ¶85).
  • Willful Infringement: The complaint alleges that Hikma had "actual knowledge" of each patent-in-suit prior to submitting its ANDA. It further alleges that Hikma's Paragraph IV certification was submitted "without adequate justification," which it contends renders the case "exceptional" under 35 U.S.C. § 285 and entitles Plaintiffs to attorneys' fees. (Compl. ¶56-57, ¶66-67, ¶76-77, ¶86-87).

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

Based on the complaint, the resolution of this case may turn on the following open questions for the court:

  • A core issue will be one of compositional scope: does the specific formulation detailed in Hikma’s confidential ANDA—particularly the average molecular weight and polymer length distribution of its excipients—fall within the precise boundaries of key claim terms like "methoxy-polyethylene glycol 350" and a polymer chain length where "n is a number in the range of 2 to 12"?
  • A second central question will concern infringement by the system: does the combination of Hikma's ANDA Product and the delivery device it intends to market constitute a "system for intranasal administration" that infringes the asserted claims of the ’495 patent, and what evidence will establish that Hikma will sell or offer to sell these components together?