API and IP Newsletter
Contents
Seven drugs likely to hit $1B in annual revenue in the next 5 years
WHO recommends two new drugs to treat COVID-19 patients – All you need to know
DMF filings in October 2021
FDA publishes list of DMF filings at the end of every quarter. We analyse DMFs by Indian companies and other companies. We study molecule selection patten of the company, we try and understand how capable are the companies to handle complex chemistry and regulatory processes. What are the chances of these companies filing ANDA? A lot of information we try to decode by DMF analysis. Every month about 70-80 DMFs are filed and 50% of those could be from Indian companies. Obviously, we cannot present all our findings but glimpses of our finding for the month of DMF filed in October 2021 are as below.
General information
Seven drugs likely to hit $1B in annual revenue in the next 5 years
Adagrasib: a drug designed to treat colorectal cancer with the KRASG12C mutation, produced by Mirati Therapeutics and Zai Lab.
Donanemab: a drug designed to slow cognitive decline, produced by Eli Lilly.
Faricimab: a drug designed to treat patients with diabetic macular edema or wet age-related macular degeneration, produced by Roche and Chugai Pharmaceutical.
Lecanemab: a drug designed to slow cognitive decline, produced by Eisai and Biogen.
Tezepelumab: an asthma drug produced by Amgen and AstraZeneca.
Tirzepatide: a drug designed to address weight loss and glycemic control, produced by Eli Lilly.
Vutrisiran: a drug designed to treat ATTR, produced by Alnylam Pharmaceuticals.
News here.
WHO recommends two new drugs to treat COVID-19 patients – All you need to know
The World Health Organization (WHO) has recommended two new drugs to treat COVID-19.
The drug Baricitinib, a selective and reversible Janus kinase 1 (JAK1) and 2 (JAK2) inhibitor, also used to treat rheumatoid arthritis is strongly recommended for patients with severe or critical COVID-19 in combination with corticosteroids.
In the same guideline update, WHO also recommended the use of the monoclonal antibody Sotrovimab in patients with non-severe COVID-19. However, it said that Sotrovimab should be administered to people at the highest risk of hospitalisation.
News here.
Intellectual Property
Fingolimod (Gilenya): CAFC decision
U.S. Court of Appeals for the Federal Circuit (CAFC) upheld US 9,187,405 (the `405) related to regimen for Gilenya. In August 2020, District Court of Delaware granted permanent injunction against HEC Pharma and HEC was restrained from launch until the expiration of the ‘405 patent ie till December 2027 (including paediatric exclusivity).
HEC Pharma was the only remaining ANDA filer challenging this patent.
Earlier, Novartis entered into settlement agreements with a number of other ANDA filers. Those ANDA filers would be able to launch fingolimod, before an undisclosed agreed date, which is prior to the expiration of `405.
OB listed patents are as below.
Gilenya (fingolimod ) is used to treat relapsing remitting multiple sclerosis (RRMS), a form of multiple sclerosis (MS). MS is a debilitating immune-mediated demyelinating disease in which the immune system attacks the myelin coating the nerves in the central nervous system. Most MS patients initially present as RRMS patients.
HEC filed an ANDA seeking approval to market a generic version of Gilenya. Novartis sued, alleging that HEC’s ANDA (partner Biocon Limited) infringes all claims of the ’405 patent
The broad claim (of `405) is as follows:
1. A method for reducing or preventing or alleviating relapses in RRMS in a subject in need thereof, comprising orally administering to said subject fingolimod, in free form or in a pharmaceutically acceptable salt form, at a daily dosage of 0.5 mg, absent an immediately preceding loading dose regimen.
In short, the ’405 patent claims methods to treat RRMS with fingolimod, at a daily dosage of 0.5 mg without an immediately preceding loading dose. A loading defined in a patent is a dose which is a higher than daily dose usually given as the first dose.
The `405 describes the results of an Experimental Autoimmune Encephalomyelitis (EAE) experiment and describes a prophetic human clinical trial (Prophetic Trial).
The district court found that HEC’s ANDA product would infringe ’405 patent
With respect to the written description for the claimed 0.5 mg daily dose, the district court found that a skilled person would understand that the inventors possessed a 0.5 mg daily dose based on one of the successful doses in the EAE experiment results. 0.3 mg/kg weekly dose.
The court credited the testimony of two of Novartis’s expert witnesses, Dr. Lawrence Steinman and Dr. William Jusko , to make the leap from a 0.3 mg/kg weekly rat dosage to a 0.5 mg daily human dosage.
The court noted that the 0.5 mg daily dose is also illustrated in the Prophetic Trial. The district court concluded that there was sufficient written description for the 0.5 mg daily dosage limitation.
With respect to the written description for the absent an immediately preceding loading dose limitation, the district court again found sufficient written description in the EAE model and the Prophetic Trial.
Neither the Prophetic Trial nor the EAE model recite a loading dose. The district court found that the Prophetic Trial describes giving a daily dosage of 0.5 mg fingolimod to treat RRMS, started initially.
The court found, crediting expert testimony, that, if a loading dose were directed, the Patent would say that a loading dose should be administered initially. Similarly, the district court found that the EAE example discloses a dosing regimen which does not involve a loading dose.
Thus, the district court concluded, the EAE model and the Prophetic Trial indicate to a person of ordinary skill that the claimed invention did not include the administration of a loading dose, and, thus, the patent provides sufficient written description of the negative limitation.
HEC appealed.
In the appeal court (CAFC) HEC argued that, as of the 2006 priority date, the inventors did not possess a 0.5 mg daily dose of fingolimod. It argued that, as of that date, 0.5 mg/day was considered too low to be effective to treat RRMS. It describes Novartis’s calculation of the 0.5 mg/day human dose as derived
The CAFC did not find HEC’s arguments convincing. The Court said, the Prophetic Trial and the EAE model provide sufficient written description to show that, as of the priority date, the inventors possessed a 0.5 mg daily fingolimod dosage as claimed in the ’405 patent.
The Prophetic Trial describes dosing RRMS patients with fingolimod hydrochloride at daily dosages of 0.5, 1.25, or 2.5 mg. The Prophetic Trial’s disclosure of two other dosages does not detract from the written description of the claimed dose.
One more argument was the term “daily dose” would not convey to a skilled artisan that no loading dose should be used. The CAFC said, the district court’s decision did not rely only on the term “daily dose”. Rather, the district court found that starting with a daily dose plainly implies that there is no loading dose as a loading dose is a larger than daily dose. Thus the CAFC agreed with district court and upheld the patent `405.
Decision here.
