API and IP Newsletter
Contents
Analysis of DMF filings in July 2021.
General information.
Pyxis IPO leads the way as four life science firms kick off 4Q, raising nearly $500M.
API price hike hits pharma units.
Intellectual Property.
Vortioxetine decision by Delaware court in USA.
Analysis of DMF filings in July 2021
We analyse DMF filings by Indian companies. This month we had looked at DMFs filed in the month of July 2021 and as expected more than 50% of total DMFs filed in July were by Indian companies. Due to space constraint, we cannot cover all DMFs filed in the month, nevertheless, some of the observations are as below.
General information
Pyxis IPO leads the way as four life science firms kick off 4Q, raising nearly $500M.
Antibody drug conjugates, or ADCs, are picking up momentum. Of the 11 drugs in this class that have been approved by the FDA, six have reached the market in the last two years. Meanwhile, new ADC companies have been busy raising money. Pyxis Oncology is one of them, emerging earlier this year with drugs and ADC technology licensed from Pfizer. Now it has $168 million in IPO proceeds to ramp up its research.
News here.
API price hike hits pharma units
The pharmaceutical industry has been battling the price rise ever since Covid hit the world. Price rise ranging from 25 per cent to 300 per cent has been registered in APIs and other raw materials from the pre-Covid era, threatening the viability of MSME units.
“The steep hike has enhanced the capital induction by three times, hitting the survival of 550 units. The situation has come to such a pass that the manufacturing of several drugs can go off the shelf if the prices are not controlled,” said president, Himachal Drug Manufacturers Association (HDMA), Rajesh Gupta.
News here.
Intellectual Property
Vortioxetine decision by Delaware court in USA
There were many ANDA filers and Lundbeck/Takeda (Innovator) sued them in Delaware Court.
The list of OB patents which were litigated:
Court opined compound patent valid & infringed, other patents valid and not infringed. So, Generics must wait till expiration of compound patent. The argumentation from both sides on compound patent is as follows:
1. The ANDA filers contend a Person of Ordinary skilled in Art (POSA) in the early 2000s would have looked to the development path a team at Wyeth took in the early 1990s to arrive at the multi-modal antidepressant venlafaxine.
2. According to ANDA filers, the Wyeth team simplified the structure of ciramadol, an older compound known to have central nervous system activity, resulting in a motif of derivative compounds structurally similar to a known antidepressant, gamfexine.
3. The ANDA filers further contend this research strategy by Lundbeck / Takeda, dubbed the “venlafaxine path,” would have been well known to a POSA.
4. A POSA in 2002, examining the prior art, would have found that three different research groups working independently to identify new antidepressants had all arrived at a common motif or scaffold, as depicted below:
5. This biarylether piperazine Dr. Lepore used as his “lead motif.” Dr. Lepore (ANDA filers’ expert) began his obviousness analysis with this “lead motif.” Dr. Lepore relied on six pieces of prior arts (ES ’127, Planas, Pinder, Kopicová, Jílek, and WO ’678) – a common structure that, he asserted, would have been the starting point for a POSA at the pertinent date seeking to develop an improved antidepressant.
6. While the Court did not reject ANDA filers’/Dr. Lepore’s analysis at the first step, the Court found a lack of clear and convincing evidence for the numerous modifications a POSA would have been required to make to Dr. Lepore’s lead motif or lead compound.
7. One reason ANDA filers had failed to persuade the Court is that Dr. Lepore did not adequately address the antidepressant landscape in 2001.
8. Beginning in the 1980s, the pharmaceutical industry had focused on developing highly-selective molecules targeting SERT inhibition.
9. A POSA at that time would have understood that greater selectivity translated into greater safety and tolerability.
10. SSRIs had by then would have become the first choice for treatment of depression because they were understood to be effective, well-tolerated, and to have a vastly superior side effect profile compared to the older TCAs (tricyclic antidepressants).
11. The ANDA filers had not presented clear and convincing evidence for why a POSA in 2001 would have preferred the ten-year-old venlafaxine path over the then current state of the art at the time of the invention viz. SSRIs and SNRIs with high-selectivity and a superior side-effect profile.
12. Despite Wyeth’s success with venlafaxine ten years earlier in the early 1990s, a POSA in 2001 would not have considered compounds with pharmacologic activity resembling TCAs (tricyclic antidepressants) or TeCAs (Tetracyclic antidepressants) as the most promising starting point for developing an improved antidepressant.
13. Dr. Lepore did not identify any improvement in activity, potency, or toxicity reasonably achievable from his proposed starting point.
14. The ANDA filers pointed to Patentee’s expert, Dr. Reider, who was working on developing of a non-SSRI antidepressant around the same time. Dr. Reider’s work, however, was done closer in time to the venlafaxine path in the mid-1990s and his work led to a failed antidepressant.
15. In the Court’s view, the evidence established that a POSA in early 2000s would have been motivated to pursue the state-of-the-art SSRIs and SNRIs at the time, rather than pursue the venlafaxine path based on older technology.
16. Dr. Reider’s failed non-SSRI antidepressant activity would only have further motivated a POSA in the SSRI direction.
17. The ANDA filers did not present clear and convincing evidence that a POSA would have selected the specific compounds from the six references which ANDA filers contend would have formed the lead motif.
18. ANDA filers had not proven by clear and convincing evidence that prior art compounds exhibited the pertinent properties “such as activity and potency, adverse effects such as toxicity, and other relevant characteristics in evidence.”
19. Accordingly, a POSA at the time of the invention would not have been motivated to select the specific prior art compounds that could have contributed to Dr. Lepore’s lead motif.
In view this the Court concluded Compound patent is valid and is infringed by the ANDA filers. Details 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.
