API and IP Newsletter

 

Contents

• Wockhardt-NCEs

• General information

• Steris discloses hundreds of ethylene oxide lawsuits over device sterilisation plant

• The critical role of data integrity in ensuring pharmaceutical quality

• Intellectual Property

• Apixaban decision: District Court of The Hague

Wockhardt-NCEs

The Wockhardt website provides information about its NCE programs. It briefly explains all five NCE programs. The website's information can be found here.

More details about the status of NCEs were presented to investors in October 2024.

The investor presentation can be found here.

The company provided its views regarding meeting endpoints in the investor presentation.

This write-up does not assess the possibility of success in Wockhardt's clinical studies. Instead, it focuses on IP and regulatory protection for some of its NCEs. In the future, clinical study experts within Sidvim may comment on the ongoing clinical studies of Wockhardt’s NCEs in different countries.

All five programs received a Qualified Infectious Disease Product (QIDP) designation in the US. A QIDP, as defined in the GAIN Act, i.e., the Generating Antibiotic Incentives Now Act (GAIN Act) of 2012. 

A drug candidate designated as QIDP can increase market protection by 5 years through GAIN exclusivity. 

Our IP and regulatory-related observations about some of their programs are as follows.

NCE	Regulatory status	IP status	Advantages
WCK 771 (EMROK) INN: levonadifloxacin, 800 mg, IV twice-daily	US: designated as qualified infectious disease product (QIDP) by US FDA due to its ability to meet unmet need in the management of serious bacterial infections India: Launched	WO2002085886A2: Basic patent family, expired  WO2005023805: Claims crystalline form and expired in many jurisdictions. IP protection for compound would expire before company could seek marketing authorisation in stringent regulatory markets.  If EMROK is approved in regulated markets, the company would rely on secondary patents such as method of use, method of administration, composition etc.	QIDP designations would provide additional 5 years exclusivity in US.  If approved in US and Europe, Emrok would enjoy 10 years of data exclusivity (plus market exclusivity) and no generic company would be able to submit the dossier to regulatory authorities during the period of data exclusivity.
WCK 2349 INN: alalevonadifloxacin, Oral	US: designated as qualified infectious disease product (QIDP) by US FDA due to its ability to meet unmet need in the management of serious bacterial infections India: Launched	WO 2007102061: Prodrug compound WO 2008053295: Oral composition In some countries IP protection till 2027.  In regulated markets there could be possibility of 5 years patent term extensions. For example, SPC in Europe and PTE in USA.	The main protection would be due to data exclusivity.  If approved in US and Europe, Emrok O would enjoy 10 years of data (and market)  exclusivity.
WCK 4873 (Miqnaf™, INN: nafithromycin)	US: designated as qualified infectious disease product (QIDP) by US FDA due to its ability to meet unmet need in the management of serious bacterial infections India: P-III trials US: -P-II trials EU: P-II trials	WO2012076989A1: Compound claim Expiration in April 2031 in US. And February 2031 in Europe WO2017122147 Composition claim One will expire in 2031 and second will expire in 2037 Patent term extensions possible.	If approval is delayed, the company would still enjoy 10 years data  ( and market) exclusivity in EU and US.

General information

Steris discloses hundreds of ethylene oxide lawsuits over device sterilisation plant

Around 275 people have filed lawsuits in Illinois state court against Steris, alleging cancer from exposure to EtO emissions into the air from a facility in the Chicago suburb of Waukegan

News here

The critical role of data integrity in ensuring pharmaceutical quality

This article explores data integrity development, its relationship to pharmaceutical quality assurance, and current implications and future developments.

News here

Intellectual Property 

Apixaban decision: District Court of The Hague

In its recent ruling, the District Court of The Hague concluded that Sandoz’s generic product infringes Bristol-Myers Squibb’s patent EP 1427415 (EP 415) and a corresponding supplementary protection certificate (SPC), valid until May 2026. 

EP 415 was in force until 16 September 2022, and the SPC entered into force on 17 September 2022 and will remain in force until 19 May 2026.

What is an SPC? The SPC (Supplementary Protection Certificate) is an intellectual property right that extends the protection of a patent for certain products in the European Economic Area (EEA).

EP 415 and the SPC cover the compound apixaban, which Bristol-Myers Squibb (BMS) markets under the Brand Eliquis. The drug thins the blood to treat thromboembolic disorders, such as blood clots, especially following hip or knee surgery.

The cited prior art was W000/39131. (WO 131)

It describes heterobicyclic Factor Xa inhibitors, of which the following is an example formula:

This formula broadly covers Apixaban. 

EP 415 (the patent under litigation) claims specifically Apixaban as below. 

A compound, which is represented by formula (1):

or a pharmaceutically acceptable salt thereof.

The monopoly that BMS has obtained with claim 1 of the patent EP 415  concerns only this one compound, i.e. Apixaban. This compound, selected by the inventors as a potential new and improved Factor Xa inhibitor, has already been disclosed in the application. 

The question that must be answered is whether the average skilled person, starting from WO 131, would arrive at the selection of the lactam-containing compound ( apixaban in EP 415) without inventive thought. 

This is evidence of the technical effect claimed by BMS: apixaban is a more potent factor Xa inhibitor than the structurally closest compounds of WO 131. BMS submitted a comparison of the Factor Xa inhibition of apixaban, expressed in Ki, with the compounds from examples 6, 10, 13, and 99 of WO 131. 

The Court said it is sufficient that one characteristic improves for an inventive selection (in this case, compared to WO 131). 

Given the aforementioned technical effect, the technical problem in assessing the inventive step of the patent based on WO 131 can be formulated as providing a compound with improved Factor Xa inhibition.

BMS argued that WO 131 does not provide pointers for this technical effect and that several steps must be taken to arrive at Apixaban of EP 415.

Sandoz has not disputed this. 

Therefore, the conclusion must be that the skilled person would only arrive at the compound in claim 1 of EP 415 with an inventive thought.

Sandoz has not disputed that this comparison demonstrates an improved effect in the sense of improved factor Xa inhibition compared to these four compounds. This means there is an improved factor Xa inhibitor compared to the relevant compounds disclosed in WO 131, and therefore, inventiveness.

The court noted the difference concerning WO 131 in the specific compound included in claim 1 of the patent, which was referred to as apixaban. 

The structural formula of apixaban is shown here again with the names of the various constituent groups added by BMS (and not disputed by Sandoz):

Hence, the court said EP 415 is inventive over prior art WO 131. 

The Court said BMS's monopoly, obtained with claim 1 of the patent, concerns only this one compound, Apixaban. The inventors selected this compound as a potential new and improved Factor Xa inhibitor, which has already been disclosed in the application (It is reproducible). This compound contributes to the state of the art. 

The outcome of the case is as follows: 

1. Sandoz is banned from selling generic versions of the blood-clot apixaban in the Netherlands until May 2026. 

2. The Court rejected BMS’ request for an advance payment of €20,000,000 in damages. 

3. The Court ordered Sandoz BV and Sandoz AG to take back all infringing products supplied by it from all its customers, other than end users, within seven days after service of this judgment.

4. The Court ordered Sandoz BV and Sandoz AG to pay an immediately due penalty of € 100,000 for each violation of, or - at BMS's discretion - for each day on which the relevant defendant acts in violation with a maximum of € 1,000,000

5. The Court ordered Sandoz jointly and severally to pay the costs of these proceedings, to date estimated on the side of BMS at € 125,000

Decision here