Minocin® (minocycline)
Case Name: Melinta Therapeutics, LLC v. Nexus Pharms., Inc., Civ. No. 21-2636, 2024 WL 4799896 (N.D. Ill. Nov. 15, 2024) (Kness, J.)
Drug Product and Patent(s)-in-Suit: Minocin® (minocycline); U.S. Patents Nos. 9,084,802 (“the ’802 patent”) and 9,278,105 (“the ’105 patent”)
Nature of the Case and Issue(s) Presented: The patents-in-suit claim the IV administration of Minocin, an aqueous solution used to treat bacterial infections. Nexus filed an ANDA, which included a paragraph IV certification to the patents-in-suit, seeking approval from FDA to market a generic version of minocycline. After a four-day bench trial, the court found that Nexus infringed the asserted claims and that those claims are valid and enforceable.
Why Melinta Prevailed: One year before trial, the parties informed the court that claim construction was not necessary. On the first day of trial that changed. The court construed the terms “composition,” “consists/consisting of,” “administering,” “injection site hemolysis,” “subject,” and “does not include magnesium” as part of its trial opinion.
The court’s infringement finding. Melinta argued that Nexus was liable for indirect infringement because the ANDA product’s label instructed a physician on how to use the product, that physician’s act of following the ANDA product label would meet the claim elements at issue in this case, thus directly infringing on the patents-in-suit. Neither the Minocin label nor the ANDA label explicitly mentions osmolality, one of the claimed limitations. But the ANDA product would inevitably have an osmolality of less than 500 mOsmol/kg due to its chemical composition. Osmolality is a property of a composition, meaning it is measured through simple calculations based on the ingredients in a composition. Therefore, just as administering Minocin will inevitably lead to an osmolality of less than 500 mOsmol/kg, administering the ANDA product will also inevitably lead to an osmolality of less than 500 mOsmol/kg. Nexus also disputed that it infringed the “injection site hemolysis” element of the asserted claims. Again, the ANDA label did not explicitly discuss injection site hemolysis. But, as with the osmolality element, injection site hemolysis reduction is a property of both Minocin and the ANDA label. “It is not a specific step that a physician who administers either product must do before injecting it into a patient; instead, hemolysis reduction is a beneficial property that all patients who receive the products will experience.” The rest of the claimed elements are found explicitly in the ANDA product label, therefore Melinta has proven direct infringement. Nexus was also liable for induced infringement. Here, evidence that the ANDA’s labeling or instructions “would inevitably lead some physicians to infringe” established the requisite intent for inducement. “Infringement of claim elements can occur when the ANDA label encourages the claimed administration of the product, even when what is claimed is not explicitly stated on the ANDA label.” Finally, because there was no substantial non-infringing use for the ANDA product, the court concluded that Nexus was also liable for contributory infringement.
The court’s finding that the patents-in-suit were not obvious. Nexus argued that Minocin was obvious in light of the combination of three prior art references: prior art minocycline; CN’268; and Gibbs. While the prior art minocycline reference taught the treatment of bacterial infections, it did so using a formulation with a much lower reconstituted pH of 2.0 to 2.8. The court also found that a skilled artisan would not be motivated to combine CN’268 and Gibbs with the prior art minocycline product. Both concern doxycycline formulations, not minocycline formulations. Second, both disclose only intramuscular formulations, not intravenous formulations. Neither mentions hemolysis or the significance of an increased molar ratio of magnesium to minocycline. Thus, Nexus had not shown by clear and convincing evidence that a skilled artisan would have been motivated to combine the prior art to create the claimed invention. The court also relied on objective indicia of non-obviousness in support of its finding, including the fact that the prior art taught away from the patents-in-suit, Melinta presented evidence of unexpected results, and that the claimed invention met a long-felt but unmet need.
The court’s finding that the patents-in-suit were not invalid under Section 112. Nexus argued that the ’802 patent was indefinite because it claimed that injection site hemolysis be reduced as compared to a formulation without magnesium, but the patent did not define injection site hemolysis or instruct how to measure it. Given the court’s claim construction of the term “injection site hemolysis,” that argument was moot. Next, Nexus argued that the patents-in-suit were not enabled and lacked adequate written description because they didn’t explain (i) the injection site hemolysis reduction claim; (ii) the pH limitations; (iii) the claimed volume range; and (iv) the osmolality range. But Nexus’s own experts testified that a skilled artisan would be able to adjust the intravenous formulation such that it would be administered at an appropriate and safe pH level, osmolality, and injection volume. “A skilled artisan would know the appropriate and safe ranges for each element and would adjust them accordingly to ensure that the administered formulation was not insoluble, toxic, or intolerable for the patient.” Therefore, a skilled artisan would not need to do an unduly amount of experimentation to discover what the appropriate pH, osmolality, and volume should be.