Nayzilam® (midazolam)
Case Name: UCB, Inc. v. Cipla Ltd., No. 21-1229-JLH, 2026 WL 1423921 (D. Del. May 15, 2026) (Hall, J.)
Drug Product and Patent(s)-in-Suit: Nayzilam® (midazolam); U.S. Patent Nos. 8,217,033 (“the ’033 patent”) and 8,809,322 (“the ’322 patent”)
Nature of the Case and Issue(s) Presented: Nayzilam is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older. The patents-in-suit claim the active pharmaceutical ingredient midazolam, a benzodiazepine commonly targeted for treating acute seizures, paired with methoxypolyethylene glycol (“mPEG”), which improves the solubility of midazolam, permeability through the nasal mucosa, sprayability, safety, and tolerability for nasal administration.
UCB sued Cipla for patent infringement arising from Cipla’s filing of an ANDA with the FDA for approval to market generic midazolam nasal spray. UCB asserted Cipla infringed claim 13 of the ‘033 patent and claim 10 of the ‘322 patent, both claiming the formulation of midazolam with mPEG. Cipla contended that the claims were invalid as anticipated and obvious. The court held a four-day bench trial, concluding that Cipla failed to prove that the asserted claims were invalid.
Why UCB Prevailed: Beginning with anticipation, Cipla relied on the Wermeling ’359 prior art reference, which claimed an intranasal formulation comprising a benzodiazepine and a nasal carrier containing 80% w/w propylene glycol. That nasal carrier was known as the Wermeling formulation. While Wermeling ‘359 recognized the exemplary use of intranasal midazolam formulations, it ded not mention mPEG by name or structure. Rather, it only disclosed intranasal midazolam formulations comprising PEG-400, propylene glycol, polyethylene glycol, or water. In explaining this omission, Cipla contended that a POSA would have understood the disclosure of “polyethylene glycol” to include mPEG by referencing another prior art reference, Tracy ’672. Tracy ’672 contained a laundry list of possible excipients and embodiments for various routes of administration that one would use to deliver medications. Tracy ’672 did indeed list mPEG as one of a dozen potential excipients that may be used specifically for intranasal administration. However, mPEG was mentioned under the heading “Viscosity Reducing Agents,” not as a proper formulation combining midazolam with mPEG. As a result, the court held that Wermeling ’359 did not disclose mPEG either expressly or inherently. Thus, Cipla did not establish that the asserted claims were anticipated.
Cipla’s obviousness defense relied on the combination of Wermeling ’359 and Carbowax, a group of thirteen PEG and three mPEG products created by Dow Chemical Company. A brochure containing information on those products discussed their use in a variety of non-pharmaceutical ways including adhesives, household products, printing and inks, and mandrel releases. However, one section described using mPEG in the pharmaceutical context, but only as a chemical intermediate rather than an excipient in an intranasal formulation.
Combining both Wermeling ’359 and Carbowax, Cipla asserted that a POSA would have been motivated to reduce the viscosity of the Wermeling Formulation (as described in Wermeling ’359) and would have tried including the excipient mPEG (as described in Carbowax). The court disagreed. The court held that neither of the prior art references would have motivated a POSA to select mPEG as an excipient for use in intranasal formulations of midazolam. mPEG had never been used in an intranasal formulation before the patent-in-suit. It has been available since the 1940s and had only been used as an ingredient in one FDA-approved topical gel. Due to this lack of use in the pharmaceutical context, the court held it was not reasonably known whether midazolam would be sufficiently soluble in mPEG, or that using mPEG in an intranasal midazolam formulation would be stable, safe, sprayable, and tolerable as of the priority date.
