API and IP Newsletter
Contents
Recent FDA approvals: Aprocitentan
We follow FDA approvals, mainly small molecules. We briefly discuss IP and chemistry. We further analyse the import-export database to understand who would be the potential generic developers and try and estimate their stage of development.
Aprocitentan was approved for medical use in the USA in March 2024. It is the first endothelin receptor antagonist to be approved by the US FDA to treat systemic hypertension.
Chemical name: (5-(4-bromo-phenyl)- 6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl}-sulfamide.
Aprocitentan, sold under the brand name Tryvio, is a medication used to treat hypertension. It is developed by Idorsia.
Aprocitentan is generically disclosed in patent family WO02053557.
A specific compound as aprocitentan perhaps first time reported in W02009024906 patent family which would be suitable for long-acting pharmaceutical compositions.
Certain manufacturing processes relating to aprocitentan are disclosed in patent family WO2015121397.
Further patent families WO2018153513 and W02019106066 relate to combinations comprising aprocitentan.
The crystalline forms of aprocitentan reported in WO2018154101A1 and in WO2023227721A1.
In US, EU and in some other jurisdictions there could be patent term extensions possible and compound per say could be protected till 2034 in Stringent Regulated Markets (SRMs).
Aprocitentan is a white to off-white powder that is insoluble in water. TRYVIO is available as film-coated 12.5 mg strength tablets for oral administration. The inactive ingredients in TRYVIO are croscarmellose sodium, hydroxypropyl cellulose, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The film coating contains the following inactive ingredients: hydroxypropyl cellulose, iron oxide black, iron oxide red, iron oxide yellow, polyvinyl alcohol, silica colloidal hydrated, talc, titanium dioxide, and triethyl citrate.
As regards to raw materials required for API synthesis, main RM which would be required is 5-(4-Bromo-phenyl)-4,6-dichloro-pyrimidine. This is the same RM required for Macitentan.
MSN, Cadila, USV, Megafine, Arva, Biocon are importing 5-(4-Bromo-phenyl)-4,6-dichloro-pyrimidine regularly. However, noticing the quantity of import, one could conclude Biocon and Arva might be developing generic aprocitentan API and could be in early phases of development.
General information
Evergreening Strategy: Extending Patent Protection, Innovation or Obstruction?
“Evergreening” in the context of intellectual property (IP), especially in the field of patents, refers to a strategy that companies often use to prolong their commercial exclusivity. This strategy is particularly common in the pharmaceutical industry, where companies secure patents for minor modifications, improvements, or new applications of existing products.
News here.
How to reskill and upskill yourself in the pharma industry
The Indian pharma sector is evolving rapidly, demanding reskilling amidst technological advancements and regulatory shifts. To thrive, professionals must embrace digital transformation, stay updated on regulations, and invest in continuous learning. Soft skills and adaptability are also crucial in navigating market dynamics. Reskilling is imperative for success in this dynamic landscape.
News here
Intellectual Property
Natco Pharma Vs Novartis AG
Pfizer Inc vs Everest Pharmaceuticals Limited
The present application seeking permanent injunction restraining infringement of patent IN 298989 has been filed on behalf of the plaintiff Pfizer Inc., a company incorporated under the laws of Delaware in the United States of America.
This application has been filed by Pfizer as part of the accompanying suit seeking permanent injunction restraining infringement of patent IN 298989 titled 'Macrocyclic Derivatives for the Treatment of Proliferative Diseases' and other attendant reliefs, in particular, restraining the defendants Everest Pharmaceuticals Limited from manufacturing, selling, distributing, promoting, or dealing with in any manner the pharmaceutical product 'LORLATINIB' either as API or any of its pharmaceutically acceptable salt under the brand name 'LORBREXEN' or any other brand name that infringes the suit patent.
Mr. Pravin Anand, counsel for Pfizer pointed out that the invention has been granted patent in 90 countries and has been approved by the US FDA on 02 November 2018; the European Medicines Agency in 2019, and in India by the Central Drugs Standard Control Organization ['CDSCO'] on 12 December 2019.
The specific compound in which the claims were granted under the suit patent is as under:
Lorlatinib is useful for treating or ameliorating abnormal cell proliferative disorders, such as cancers, in this case particularly, for lung cancer.
The said compound is marketed and sold commercially by Pfizer under the tradename 'LORBRIQUA®', of which 'LORLATINIB' is the active pharmaceutical ingredient.
The grievance is against the defendants Everest Pharmaceuticals Limited who are found to be selling the 'LORBREXEN' [infringing product] containing the same compound 'LORLATINIB'.
Everest Pharmaceuticals Limited is a company incorporated under the authority of People's Republic of Bangladesh, however, selling the infringing product in India through various channels including e-commerce portal Indiamart.
The suppliers at Indiamart were also found to have bid for a tender for supplying the infringing product at the Military Hospital, Bhopal, Command Hospital, Lucknow etc. The concerned bid documents have been appended by Pfizer.
Mr. Anand, counsel for Pfizer pointed out that Everest Pharmaceuticals Limited has not been granted any licence to manufacture, sell, or import the product in India. This is evident from a Right to Information application filed by Pfizer Inc before the CDSCO to which a response was received stating that no application had been received for manufacturing and importing of the drug 'LORLATINIB' marketed under the name 'LORBREXEN' manufactured by Everest Pharmaceutical Limited. Further that they had not granted any registration and certificates and import licence for that drug in favour of Everest Pharmaceutical Limited.
Mr. Anand, Counsel for Pfizer Inc further pointed out to licence which has been granted in favour of Everest Pharmaceuticals Limited which is dated 18 January 2023; granted by the Government of Bangladesh for the territory of Bangladesh.
The Counsel stated, Pfizer Inc is also further taking steps to communicate to various Customs Authorities in order to alert them of the illegal import of the said product. It is pointed out that there have been earlier infringement actions by Pfizer Inc against Everest Pharmaceuticals Limited . Attention is drawn by Mr. Anand to the injunction granted by this Court in in Pfizer Inc. & Ors. v. Everest Pharmaceuticals Limited, on 04 May 2020.
In view of the above facts and circumstances, the Court is satisfied that Pfizer Inc had made out a prima facie case for grant of an ex-parte ad interim injunction till the next date of hearing. The balance of convenience lies in favour of Pfizer, and they are likely to suffer irreparable harm in case the injunction, as prayed for, is not granted.
Accordingly, until the next hearing date, an ex-parte ad interim injunction is granted in favour of Pfizer and against defendant Everest Pharmaceuticals Limited.
Decision here
