DMF filings in January 2025 and the CAFC's decision on Invega Trinza (paliperidone palmitate-PP3M)
Contents
Recent DMF filings
General information
Bitter pill for Lupin, Zydus Life shares as patent case over Myrbetriq lost in US court
Novartis and Accord settle UPC dispute over drug administration with apple sauce
Intellectual Property
Janssen vs. Mylan: CAFC's decision on Invega Trinza (paliperidone palmitate-PP3M)
Recent DMF filings
We track DMFs filed each month. The FDA publishes the list of DMF filings quarterly. The first quarter DMF filing list was released in the first week of April, and this month we are analysing DMFs filed in January 2025.
A total of 81 DMFs were filed in January 2025. The top DMF filers are listed below.
About 40 DMFs were filed by Chinese companies, and about 32 DMFs were filed by Indian companies. The Chinese have overtaken Indian companies in the DMF filing list for some time now.
Some of our other observations are as follows.
General information
Bitter pill for Lupin, Zydus Life shares as patent case over Myrbetriq lost in US court
This case was regarding US 10842780, related to the sustained release formulation of mirabegron. "The Court concludes the Generics Manufacturers did not prove their asserted invalidity defences by clear and convincing evidence," the Delaware District Court's ruling dated April 15 said. In this case, the 'Generics Manufacturers' are Zydus and Lupin.
Novartis and Accord settle UPC dispute over drug administration with apple sauce
The dispute centred on Novartis’ patent EP 2 501 384, which protects a method of treating proliferative disorders and other pathological conditions mediated by BCR-ABL, C-KIT, DDR1, DDR2 or PDGF-R kinase activity. In simpler terms, it protects the administration of nilotinib together with apple sauce.
According to JUVE Patent information, the case has now concluded as the parties have reached an amicable settlement. The details of the agreement are confidential.
News here
Intellectual Property
Janssen vs. Mylan: CAFC's decision on Invega Trinza (paliperidone palmitate-PP3M)
Overview
The United States Court of Appeals for the Federal Circuit (CAFC) heard a case involving Janssen Pharmaceuticals, Inc., Janssen Pharmaceutica NV, and Janssen Research & Development LLC (collectively, Janssen) against Mylan Laboratories Ltd. (Mylan). Janssen sued Mylan for patent infringement, claiming that Mylan's generic version of Janssen's Invega Trinza product would violate U.S. Patent No. 10,143,693 (the '693 patent). The district court determined that Mylan would induce infringement and that the '693 patent was valid. Mylan then appealed this decision. The Court of Appeals upheld the district court's ruling.
Invega Trinza (PP3M) is an injection administered four times a year, making it the longest-acting schizophrenia drug available. However, patients must use the once-a-month dosing option (PP1M) for at least four months before transitioning to Invega Trinza.
Invega Trinza is a blockbuster product for Janssen, although recent information regarding its sales is not publicly available; in the U.S., it could be a USD 2.5 billion product.
OB listed patent
Background
The '693 patent describes a method for treating patients who have missed a treatment with the 3-month paliperidone palmitate extended-release injectable suspension formulation (PP3M). Janssen is an MA holder of FDA-approved PP3M for treating schizophrenia. The patent claim pertains to a dosing regimen for administering an injectable paliperidone palmitate depot to a patient requiring treatment for psychosis, schizophrenia, or bipolar disorder who has been treated with PP3M but has missed an injection for 4 to 9 months. The regimen involves administering an initial re-initiation loading dose of PP1M (1-month paliperidone palmitate) intramuscularly in the deltoid muscle, followed by a second re-initiation loading dose of PP1M approximately 4 to 12 days after the first dose. Finally, a re-initiation dose of PP3M is administered intramuscularly in the deltoid or gluteal muscle approximately 23 to 37 days after the second PP1M dose.
Mylan filed ANDA seeking FDA approval to market a generic version of Janssen's Invega Trinza before the '693 patent's expiration. Janssen initiated the lawsuit, asserting that Mylan's proposed ANDA labels would induce healthcare providers (HCPs) to infringe the '693 patent. Mylan responded that the '693 patent was invalid.
The technology here concerns paliperidone palmitate (PP), an antipsychotic used to treat schizophrenia. PP comes in at least two long-acting injectable forms—one that lasts for one month (PP1M) and another that lasts for three months (PP3M). The difference between the two products, PP1M and PP3M, is as follows.
District Court Decision
After an eight-day bench trial, the district court held that Janssen demonstrated by a preponderance of the evidence that Mylan would inevitably induce HCPs to infringe the asserted claims of the '693 patent. The court also found that Mylan had not demonstrated by clear and convincing evidence that the '693 patent was obvious or otherwise invalid.
Issues on Appeal
Mylan raised two main issues on appeal:
1. The district court incorrectly found that Mylan would induce infringement of the asserted claims.
2. The district court incorrectly found that the asserted claims were not invalid for obviousness.
Court of Appeals Analysis
I. Induced Infringement
Mylan argued that it could not induce infringement because its proposed ANDA labels specifically discourage patients from missing doses. It also contended that Janssen failed to prove that infringement would "inevitably" occur, as it did not establish that patients who missed a dose would return and complete the claimed reinitiation regimen. Lastly, Mylan asserted that because the asserted claims involve two parties—a doctor and a patient—this creates a divided-infringement issue, thus undermining Janssen's case for direct infringement.
The Court of Appeals found Mylan's arguments unpersuasive.
• Specific Intent to Induce Infringement: The court noted that to prevail on a theory of induced infringement, Janssen must prove (1) direct infringement and (2) that the ANDA applicant has the specific intent to induce infringement. The court found that Mylan's proposed ANDA labels explicitly instruct HCPs to reinitiate patients onto PP3M using the asserted claims' methodology. The labels state that to manage missed doses, HCPs should refer to the Full Prescribing Information, which instructs them to use the re-initiation regimen shown in Table 2. The court concluded that these explicit instructions establish specific intent for induced infringement.
• Inevitable Infringement: The court concurred with the district court's determination that missed doses and patients returning between four and nine months after a missed dose are inevitable, indicating that the infringement of the claimed reinitiation regimen would also be unavoidable (inevitable). The court cited Mylan's expert testimony, which recognised that more than 50% of Invega Trinza patients have missed a dose, with 20 to 30% returning for an appointment 16 weeks or more (approximately four months) after the missed dose.
• Divided Infringement: Mylan argued that under a divided-infringement theory, it could not induce infringement because the claimed dosing regimen would be executed by two parties—the patient and the healthcare provider—resulting in no direct infringement and, consequently, no inducement. The Court of Appeals rejected this argument, determining that Mylan's divided-infringement defence was untimely since it was not disclosed in its contentions and appeared improperly for the first time in Mylan's rebuttal expert report.
II. Obviousness
Mylan contested the district court's determination of nonobviousness, arguing that the claimed PP3M reinitiation regimen is apparent (obvious) in light of the prior-art PP1M regimen and that the prior art taught the specific four-to-nine-month reinitiation window asserted in the claims.
The Court of Appeals rejected Mylan's arguments.
- Motivation to Use PP1M After PP3M: The court concurred with the district court's determination that nothing in the prior art motivated a skilled artisan to use PP1M after a patient was advanced to PP3M. The court observed that the '693 patent was the first long-acting injectable antipsychotic to recommend using two different long-acting injectable formulations to manage a missed dose.
- Prior Art Teaching of Reinitiation Window: The court found that while the prior art indicated starting a patient on PP1M to reach PP3M, it advocated for stabilising on PP1M for at least four months before progressing to PP3M. This contrasted with the asserted claim's reinitiation dose of PP3M approximately 23 to 37 days after the second reinitiation loading dose of PP1M. The court concluded that if a patient missed a PP3M dose and was given PP1M, there would have been no reason or motivation to advance them to PP3M without first stabilising them on PP1M for at least 17 weeks, as this was the sole method reportedly used for PP3M in the prior art.
Conclusion
The Court of Appeals (CAFC) deemed Mylan's remaining arguments unpersuasive. The court upheld the district court's decision regarding induced infringement and non-obviousness.
Decision Here
