Recitation of a “stable” formulation of the anti-cancer injectable cyclophosphamide doomed an Ingenus Pharmaceuticals patent on Friday, with the term deemed indefinite. In the same decision, a US judge in Illinois denied the patent owner's request for a summary judgment of infringement. That not only clears a path for Nexus Pharmaceuticals to enter the market with its FDA-approved generic, but also leaves a Dr. Reddy's subsidiary — who last summer agreed to commercialize Ingenus' product in the US — in limbo.
Nexus Pharmaceuticals’ efforts to compete in the anti-cancer arena took a big step forward Friday when a patent associated with injectable cyclophosphamide was declared invalid.According to US Judge Mary M. Rowland of the Northern District of Illinois (see here), “stable” — as the term appears in all four claims of Ingenus Pharmaceuticals’ US Patent No. 10,993,952 — is indefinite because it fails to inform a person of skill in the art, or POSA, with reasonable certainty of the “test or conditions a similar invention could be said to infringe.”
Central to her conclusion was agreed-upon testimony from experts for both parties that a POSA would “generally” understand references to stability of cyclophosphamide to involve degradation, impurity formation, decomposition, solution stability and storage stability.
Those same experts also reached consensus on several “aspects” of stability in reference to cyclophosphamide, specifically, such as the ability to control impurities within acceptable limits and the ability to remain stable when stored at 2-8 degrees Celsius.
“The question, then, is not whether ‘stable’ has a singular definition; the question is whether the patent provides a POSA notice of what is claimed by the word ‘stable’ such that a POSA can know when they risk infringement,” Rowland explained.
“On this front, Nexus has established by clear and convincing evidence that an impermissible ‘zone of uncertainty’ exists,” she ruled.
At issue in the dispute is Nexus’s abbreviated new drug application, or ANDA, for an intravenous formulation of cyclophosphamide, ethanol, propylene glycol, polyethylene glycol and monothioglycerol.
Cyclophosphamide can be used to treat a variety of cancers, including ovarian, retinoblastoma, multiple myeloma and more.
The US Food and Drug Administration gave Nexus the go-ahead in October 2024, two years after Ingenus and India’s Leiutis Pharmaceuticals filed the instant suit. Post-complaint, Leiutis assigned all rights in the technology to Ingenus, leading to Leiutis’s dismissal from the case on May 6 for lack of standing.
Rowland on Friday also addressed claims by Ingenus that the US Supreme Court’s 2015 decision in Commil v. Cisco and the US Court of Appeals for the Federal Circuit’s 2003 decision in Pandrol v. Airboss stand for the notion that infringement can be considered separate and apart from validity.
Ingenus staked out that position in arguing that the judge could, and should, reach the question of whether the Nexus ANDA infringes, regardless of her findings on invalidity.
But Rowland said neither case goes as far as the plaintiff suggests.
In Commil, the Supreme Court considered only whether a defendant’s belief that a patent is invalid can serve as a defense to claims of induced infringement; meanwhile, in Pandrol, the Federal Circuit addressed what Rowland called an equally narrow question, “of whether an alleged infringer waived its ability to raise invalidity as a defense by failing to raise it in response to the patentee’s motion for summary judgment for infringement.”
Crucially, however, she noted the Pandrol court “did not hold that an infringement claim can succeed when the underlying patent is invalid.” Moreover, she said, “several other cases make clear that a patent cannot be infringed unless its terms are defined.”
Only a valid claim can be infringed, per binding Federal Circuit precedent in 2021 in Viskase v. Am. Nat. Can. Co., Rowland ruled.
Because all claims of Ingenus’s patent “implicitly or explicitly” contain the indefinite term “stable,” she said the patent owner is unentitled to summary judgment.
That marks a blow to Ingenus, who last summer announced a partnership with the US subsidiary of India’s Dr. Reddy’s Laboratories to commercialize in the US ready-to-deliver formulations of cyclophosphamide injection at 500 mg/2.5mL; 1g/5mL; and 2g/10mL strengths. In the announcement, Dr. Reddy’s USA and Ingenus revealed a 50-50 profit share.
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