API and IP Newsletter
Contents
FDA approvals in the month of June 2021.
General information.
Nepali pharmaceutical companies mull setting up vaccine plants.
WHO's Solidarity trial will test three new potential COVID-19 drugs in a new phase.
Intellectual Property.
FCM vs Natco (and Best Crop)
FDA approvals in month of June 2021
Below are the approvals for the month of June. We covered the chemistry of Finerenone last week. We will be covering the chemistry of the remaining small molecules in this and few subsequent Newsletters.
This week let us look at chemistry of Belumosudil (SLx-2119)
Example 82 in WO2008054599A2 specifically covers 2-(3-(4-(lH-indazol-5-ylamino) quinazolin-2-yl)phenoxy)-N-isopropylacetamide (Belumosudil)
1. A suspension of 2-(3-(4-(lH-indazol-5-ylamino)quinazolin-2- yl)phenoxy)acetic acid (70 mg, 0.14 mmol), PyBOP® (40 mg, 0.077 mmol), DIEA (24 μL, 0.14 mmol) in dry CH2Cl2 : DMF (2 : 0.1 mL) was stirred at RT for 15 minutes.
2. To this solution of activated acid was added propan-2-amine (5.4 mg, 0.091 mmol).
3. After 30 minutes, 1.0 equivalent of DIEA and 0.55 equivalents of PyBOP® were added.
4. After stirring the solution for 15 minutes, 0.65 equivalents of propan-2-aminewere added and the mixture was stirred for an additional 30 minutes.
5. The solvent was removed in vacuo and the crude product was purified using prep HPLC (25-50_90 mins) to afford 2-(3-(4- (lH-indazol-5-ylamino)quinazolin-2-yl)phenoxy)-N-isopropylacetamide. (40 mg, 0.086 mmol, 61%).
This must be the first synthesis of Belumosudil reported in the literature.
Compounds and processes are reported in patent families WO 2006105081(covered but not disclosed?), WO 2008054599, WO 2010104851, and WO 2012040499. The route was also reported in WO 2014055996 and WO 2015157556.
General information
Nepali pharmaceutical companies mull setting up vaccine plants
A number of Nepali pharmaceutical companies have approached the Department of Drug Administration after the government announced incentives for firms that produce vaccines for infectious diseases including Covid-19.
The government came up with the incentive package considering that countries without access to vaccines have suffered badly during the Covid-19 pandemic. (Read more)
WHO's Solidarity trial will test three new potential COVID-19 drugs in new phase
The World Health Organization's (WHO) Solidarity PLUS trial will be entering its second phase. It will be testing four new therapies - artesunate, imatinib and infliximab - to treat COVID-19 .
Four drugs - remdesivir, hydroxychloroquine, lopinavir and interferon - were evaluated during a previous Solidarity PLUS trial where they found that they had "little or no effect on hospitalized patients with COVID-19."
These drugs were chosen by an independent expert panel as they could reduce the risk of death in patients hospitalized for COVID-19 . The manufactures of these drugs were donated for the trials.
Intellectual Property
FCM vs Natco (and Best Crop)
The Delhi High Court allowed FMC interim injunction against Natco Pharma Ltd (and Best Crop Science LLP).
The injunction was for marketing of FCM’s insecticide Chlorantraniliprole (CTPR). Please note this litigation is for injunction, and other core issues would be litigated in the upcoming trial.
The case revolves around “disclosure” and “coverage”. This Newsletter earlier also reported many such type of litigations. In most of the cases, there will be first genus patent application covering Markush claim.
This patent/Markush claim would comprise millions of compounds, later innovators would file another patent application claiming specific compounds, which would have the desired activity.
In India innovators will invariably struggle to seek protection for specific compound patents, i.e., selection patents. In India, there is no specific provision in the Act for the selection of patents.
The main question before the Court was, merely because the Markush formula covered the CTPR (in prior art, Indian Patent 204978), did this automatically lead to the conclusion that the CTPR is disclosed by the prior art?
In Novartis judgement, the Supreme Court of India was not much inclined to accept the differences between ‘coverage’ and ‘disclosure’.
The key argument raised by Natco was that CTPR was disclosed in the genus patent IN 204978.
Natco and co argued, when the preferred embodiments from the complete specification of the genus patent (IN 204978) are applied to the concerned Markush structure, it led to CTPR.
The court pointed out that for a determination on obviousness it must be seen whether a person skilled in the art would have reached the specific patent (IN 201307) from the genus patent (IN 204978) “without unduly straining his imaginative and creative faculties”.
In this context, the court noted that Natco cherry picked specific substitutions from the millions of possibilities in the Markush structure in IN 204978 to arrive at CTPR. The Court remarked, Natco’s argument is based on hindsight analysis, and a person skilled in art must do a lot of experimentation to arrive at CTPR from IN 204978.
Hence, the Hon Court concluded, in the present case, no coverage and no disclosure, by FCM, of CTPR in the genus patent IN 204978.
FMC succeeded in receiving an injunction for Chlorantraniliprole. Very long, 175 page decision is here.
This is going to be an interesting case and few other facts would be discussed at further trial. We will follow up and report in subsequent Newsletters.
Disclaimer
Sidvim LifeSciences Private Ltd has taken due care and caution in developing this document. Since the data used for analysis in this document is based on the information available in the public domain, its adequacy or accuracy or completeness cannot be guaranteed. This document is for information only and Sidvim is not responsible for losses that may or may not arise due to any decisions made based on the same. No part of the document shall constitute or be represented as a legal opinion of any kind or nature. No warranties or guarantees, expressed or implied, are included in or intended by the document, except that it has been prepared in accordance with the current generally accepted practices and standards consistent with the level of care and skill exercised under similar circumstances by professional consultants or firms that perform the same or similar services.
