API and IP Newsletter
Contents
FDA approvals in February 2021.
General information.
Pharma R&D: Taking the digital route.
Cyclica’s AI-based drug discovery platform achieves over 60% of actionable hits for its pharma clients.
Intellectual Property.
FDA approvals in February 2021
In this Newsletter we cover synthetic APIs, small molecules approval every month. The more emphasis on synthesis of APIs than anything else. Other aspects of the drugs, such as mechanism of action, method of use, method of administration etc. are generally not covered. This week we will cover Umbralisib.
Umbralisib
U.S. Patent No. 9,150,579 discloses umbralisib and pharmaceutically acceptable salts. Tosylate salt (marketed salt) is individualised as 4-Methylbenzenesulfonate Salt of Compound B1
(S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one 4-methylbenzenesulfonate. (Tosylate salt of umbralisib)
(S)-2-(1-(4-amino-3-(3-fluoro-4-isopropoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-6-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one 4-methylbenzenesulfonate:
To umbralisib (22.7 g, 39.69 mmol) in isopropanol (600 ml), p-toluenesulphonic acid (8.30 g, 43.66 mmol) was added and refluxed for 1 h. The reaction mixture was concentrated, co-distilled with petroleum ether and dried. To the residue water (300 ml) was added and stirred for 30 min. The solid was filtered, washed with petroleum ether and dried under vacuum to afford the title compound as off-white solid (28.2 g, 95%).
MP: 138-141° C. 1H-NMR and Mass: 572.4 (M++1-PTSA) are reported.
Enantiomeric excess: 93.4% as determined by HPLC on a chiralpak AD-H column, enriched in the fast eluting isomer (retention time=12.35 min.)
US 9,969,740, US 10,414,773 and US 2019/0382411 disclose solid state forms of tosylate salts of umbralisib.
Alembic Pharmaceutical is exporting FDF samples to US. Could it be for BA/BE studies? It indicates, company is very active in umbralisib and could be ahead of a curve to be able to file the ANDA on NCE-1 date.
General information
Pharma R&D: Taking the digital route
In India, Novartis has a digital hub called Biome India, which is aimed at establishing a network between Novartis and external partners from across the digital ecosystem. This is the first such hub in Asia
(here)
Cyclica’s AI-based drug discovery platform achieves over 60% of actionable hits for its pharma clients
Traditional in silico approaches to drug screening tend to focus on a single protein target paradigm (potency), but compounds will actually hit multiple targets in the body. This can lead to off-target effects such as efficacy and toxicity issues, which could cause these drugs to fail early preclinical or clinical testing.
Matchmaker, in 2018. The platform allows for proteome-wide evaluation to determine complex drug polypharmacology in real time, meaning it predicts the on-target and off-target interactions that these compounds can have in vivo.
News here.
Intellectual Property
Sun Pharmaceuticals Vs Lupin
I was doing usual reading for searching interesting cases in recent past for my weekly post. Somewhere I read, this could be the first ANDA litigation between two Indian Companies!! I found this very interesting (encouraging?) and thought of bringing this to the notice of readers of this Newsletter.
Sun Pharma Vs Lupin!!! This is regarding BromoSite. API bromofenac.
Bromsite is a small product, peak sales estimated is 40-50 mio usd as per analyst report. (here). Sun Pharma is the innovator.
Only one patent listed in OB. US 8778999
Independent claim is as below:
1. A topical ophthalmic composition formulated for application to the eye, said composition comprising a therapeutically effective amount of bromfenac and a flowable crosslinked carboxy-containing polycarbophil mucoadhesive polymer, wherein the composition has a viscosity in the range of about 1,000 to about 3,400 cps and a pH of about 7.4 to about 8.5.
BromSite is used to treat and prevent ocular pain associated with cataract surgery. Lupin filed ANDA. Sun sued Lupin for infringement, claiming that Lupin’s generic version contain chemically identical bromofenac ophthalmic solution in the same proportion of 0.075%, with the same viscosity
Lupin argued
1. They have different viscosity
2. US 8778999 is not valid
3. Dr. Lyle Bowman, who helped to prosecute US 8778999 committed inequitable conduct by failing to submit certain prior art he invented.
Both the parties tried to settled but failed. The matter was before the court for pretrial motions to exclude or preclude expert testimony and reports.
Sun wanted court to remove Carmichael's Report. According to Sun, Carmichael offers improper opinion evidence on substantive patent law.
Lupin requested to exclude Dr. Olejnik's opinions on "'gelation' of ophthalmic compositions on the grounds that Dr. Olejnik is unqualified and unreliable.
Court agreed to Sun to strike the Carmichael report. Lupin’s motion to exclude certain opinions of Dr. Olejnik is denied in part with respect to anticipation and obviousness, but Hon. Judge would like to hear Dr. Olejnik opinion on gels/gelation during the trial.
This matter is now scheduled for trial in this month. We will cover the decision once it is handed down.
More details are here.
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.
