API and IP Newsletter
Content
Analysis of imports of Alembic.
General information.
Will drug prices decrease for Medicare recipients? Pharmaceutical industry says no.
Five pharma cybersecurity breaches to know and learn from..
Intellectual Property.
Apixaban -USA, CAFC decision and impact on generic launches.
Analysis of imports of Alembic
In our firm, we analyse development portfolios of many companies based on public domain information such as patent application filings and import-export database etc. This week we chose Alembic.
There are several entries in the database and to cover all those in such a small sized newsletter would be an impossible task. Only a few of the entries have been reported here as a gist of our findings. Our conclusions are summarized in the SIDVIM comments column below.
General information
Will drug prices decrease for Medicare recipients? Pharmaceutical industry says no
The pharmaceutical industry sent a letter to Congress this week that explained they could not let Medicare bargain on prices of medications for the millions of people they cover because it would give the government too much power. The response from the pharmaceutical industry is that the government’s attempts at gaining control of pricing is a smokescreen to gain control and would diminish patients access to medications. (Read more)
Five pharma cybersecurity breaches to know and learn from
2014: Dragonfly attack on pharma suppliers
2017: NotPetya attack on Merck
2018-19: Winnti attacks on Bayer and Roche
2020: Data breach at Dr Reddy’s Laboratories
2020: Attacks on Pfizer/BioNTech and AstraZeneca
Intellectual Property
Apixaban -USA, CAFC decision and impact on generic launches.
Based on OB listed patents innovator was expecting generic formulations to appear in the U.S between 2026 and 2031. The Brand settled with numerous generic drug companies for April 2028 date, however, Sunshine, Sigmapharm, Unichem and a couple of others (Gxs) were still litigating their cases.
Bristol-Myers Squibb / Pfizer Inc. (Brand) sued Gxs for infringement of US 6,967,208 (compound patent – expiring on 21 November 2026) and US 9,326,945 (composition patent – expiring on 24 February 2031). Gxs alleged that the asserted claims of both the '208 (claims 13 and 104) and '945 (claims 21 and 22) patents are not infringed and invalid.
Infringement:
1. Sigmapharm’s ANDA:
Sigmapharm used crystalline Form I of apixaban as the starting material for their apixaban tablet. It used process where crystalline Form I was dissolved in solution with povidone & then it was sprayed, dried to make amorphous solid dispersion.
With respect to US’208 patent, Sigmapharm argued that claim 1 of the patent on which claim 13 & claim 104 depend does not cover apixaban. Court found that claim 1 covers apixaban & therefore Sigmapharm’s ANDA infringes dependent claim 13.
With respect to US’945 patent, Sigmapharm argued that BMS failed to prove that its ANDA product contains crystalline apixaban and crystalline apixaban having claimed particle size. But the court said that BMS expert, Dr Atwood identified four characteristic crystalline apixaban peaks at 12.3, 12.9, 27.1 & 22.1. In defence, Sigmapharm contended that its expert, Dr. Zaworotko’s XRPD testing revealed no evidence of crystalline apixaban. Court, however, said that Dr. Atwood’s method was more sensitive than Dr. Zaworotko because Dr. Atwood used count times of between 30 and 100 seconds. Sigmapharma finally argued that even if some of the apixaban in its ANDA product is crystallized, there is no “apixaban particle” as required by claims but rather “composite particles consisting of PVP-apixaban bonded together”. Court, however, said that Sigmapharma has not shown that such composite particles do not contain crystalline apixaban particles. Thus, the court concluded that any crystalline apixaban in Sigmapharma’s ANDA product consists of crystalline apixaban particles.
With respect to particle size limitation (D90 less than 89 µm), Sigmapharm , BMS has proved Sigmapharm’s ANDA has crystalline apixaban particles with D90 equal or less than 89 µm & thus it infringed US’945 patent.
2. Sunshine’s ANDA:
Sunshine also used a similar process where amorphous dispersion was formed using crystalline apixaban & povidone. Court here also said that BMS has proved by preponderance of the evidence that Sunshine’s ANDA product contains crystalline apixaban particles.
3. Unichem’s ANDA:
Unichem manufactured its ANDA product by Fluidized bed process. First dry excipients were fed into a fluidized bed granulator. In parallel, starting apixabam API was dissolved in volatile solvents such as methylene chloride and IPA. Then this solution was sprayed onto the surface of excipient particles floating in the fluidized bed granulator. Thus, volatile solvents evaporated leaving behind small apixaban particles deposited on excipient particles. After granulation, subsequent steps were undertaken to form a tablet. The only limitation Unichem disputed was particle size limitation.
BMS expert, Dr. Berkland analysed ANDA product using SEM-EDS technique. After observing 68 granules containing thousands of apixaban particles, he determined that all of the particles were 1 µm in size. Therefore, crystalline apixaban in Unichem’s ANDA product had D90 equal to or less than 89 µm. Dr. Berkland opined that his conclusions were consistent with Unichem’s manufacturing process which causes evaporation of volatile solvents leaving behind small apixaban particles
Invalidation:
With respect to invalidation, Gxs put forth various attacks such as improper dependency, lack of enablement, lack of written description and obviousness. But, the court found that Gxs failed to prove that asserted claims are invalid.
On 05 August 2020, Delaware Court found compound and composition patents valid & infringed by ANDA filers (Gxs)
Detailed article here
Matter was in Appeal Court (CAFC), On 03 September 2021, Federal Circuit (CAFC) affirmed Delaware district court’s decision.
With this CAFC decision, the earliest that generic manufacturers are permitted to launch their apixaban products would be in April 2028.
Decision 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.
