cyclophosphamide solution for injection
Case Name: Ingenus Pharms., LLC v. Nexus Pharms., Inc., No. 22-cv-02868, 2025 WL 1359357 (N.D. Ill. May 9, 2025) (Rowland, J.)
Drug Product and Patent(s)-in-Suit: cyclophosphamide solution for injection; U.S. Patent No. 10,993,952 (“the ’952 patent”)
Nature of the Case and Issue(s) Presented: Cyclophosphamide is an antineoplastic agent used to treat various cancers, including lymphomas, myeloma, leukemia, and breast carcinoma. The ’952 patent, issued to Plaintiffs in May 2021, claims a “stable liquid parenteral formulation” of cyclophosphamide. The patent describes two primary conditions under which the formulation was evaluated for stability: “refrigerated conditions” (2-8°C) and “accelerated conditions” (40°C/75% RH). The patent prosecution history shows that the examiner initially rejected the claims as obvious over prior art formulations. The patent ultimately issued only after the applicants argued that their formulation demonstrated superior stability based on reduced impurity formation and minimal potency loss under stress testing, e.g., 40°C.
Ingenus sued Nexus alleging patent infringement of the ‘952 patent after Nexus submitted its ANDA with FDA. The parties filed cross-motions for summary judgment. Ingenus moved on its infringement claim and Nexus moved on the basis that the ‘952 patent was invalid for indefiniteness under 35 U.S.C. § 112, based on the use of the term “stable” in all asserted claims, particularly given the existence of different types of stability testing and varying interpretations of what “stable” means in the pharmaceutical context. The court denied Ingenus’s motion and granted Nexus’s motion.
Why Nexus Prevailed: With respect to its finding that the ’952 patent is invalid as indefinite, the court reasoned that the term “stable” failed to inform a POSA with reasonable certainty about the scope of the claimed invention. The court noted that the patent mentions two testing paradigms: accelerated conditions (40°C/75% RH for one week) and refrigerated conditions (2–8°C), but it does not clarify which set of conditions is required to satisfy the “stable” limitation, nor does it specify what impurity levels, timeframes, or endpoints define such stability under either paradigm.
Compounding this discrepancy was the conflicting and evolving interpretations offered by Ingenus’s own expert. Initially, the expert asserted that infringement would require demonstrating stability under both refrigerated and accelerated conditions. Later, he reversed that view, stating that a “POSA would be sure whether their product is in or outside the scope of the patent’s claims because stability under Refrigerated Conditions ‘is not claimed,’ and the product would only need to satisfy the definition of stability under the Accelerated Conditions Test to infringe.” At his deposition, he once again contradicted his prior statements and “changed his opinion again, arguing that the patent did claim stability under Refrigerated Conditions.” To the court, the expert’s ever changing opinions demonstrated that the patent lacked clear, objective boundaries and reinforced its finding that the term “stable” created a “zone of uncertainty.” The court also emphasized that the patent provided insufficient guidance about how a POSA should assess stability under refrigerated conditions. For instance, while the patent referenced refrigerated storage, it failed to identify the test duration, acceptable impurity thresholds, or precise impurities to be measured.
The court analogized this case to the Federal Circuit’s decision in Teva Pharms. USA, Inc. v. Sandoz, Inc., where the term “molecular weight” was held indefinite because it could be measured in multiple ways, each producing different results, and the patent failed to identify which method to use. Likewise, in HZNP Medicines LLC v. Actavis Labs., the Federal Circuit affirmed indefiniteness where a term (“better drying time”) could be assessed using multiple, inconsistent tests. Here, the court found that “stable” similarly could be tested in multiple ways, yielding divergent results, and that neither the claims, specification, nor prosecution history resolved this ambiguity.
The court’s finding of invalidity lead to the denial of Plaintiffs’ motion for summary judgment of infringement. “In short, because an invalid claim can not be infringed, and because all the claims in the ‘952 Patent either implicitly or explicitly contain the indefinite term ‘stable,’ Ingenus’s motion for summary judgment is denied” (internal citations omitted).
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