API and IP Newsletter

 

Contents

• Analysis of imports by Glenmark

• General information

• Strengthening regulatory framework, India to join the global quality scheme

• Manufacturing Technology Trends

• Intellectual Property

• The court’s decision favours Merck in Sugammadex and the complexity associated with Patent term extension.

Analysis of imports by Glenmark

We analysed patent applications filed by Glenmark last week. That was primarily to understand what they are developing in their development centre and to analyse the company’s long-term plan.

This week we analysed their imports and tried to substantiate our inference from the IP analysis last week. Glimpses of our observations are as below. 

Import by Glenmark	Qty in KG	Sidvim Comments
BROMIDE  TIOTROPIUM	0.01	Glenmark is importing tiotropium bromide in small lots from Chemo Iberica in Italy. This could be for their potential 505 (b) (2) application to deliver the drug through a nebuliser, which is different from the marketed meter dose formulation. Glenmark had filed a patent application WO2023031753A2 for this modified dosage form.
DIMETHYL 3-OXO-1,3-DIHYDROISOBENZOFURA N-1-YL PHOSPHONATE	1.00	These are intermediates for Olaparib. It seems Glenmark will file DMF soon. Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. In Olaparib, there are a couple of challenging formulation patents. Those to be circumvented. There's a possibility that Glenmark could be developing a formulation and would file ANDA.
N-CYCLOPROPYLCARBONYL PIPERAZINE	1.00
2-FLUORO-5-FORMYLBENZONITRILE	1.00
2,6-DIFLUORO-BENZYL CHLORIDE	1.00	These are intermediates for Relugolix. Glenmark could be working on filing DMF of reluglox. There are two other DMFs filed for Relugolix and Glenmark could join them soon. Relugolix, sold under the brand names Orgovyx and Relumina, among others, is a gonadotropin-releasing hormone antagonist (GnRH receptor antagonist) medication that is used in the treatment of prostate cancer in men and uterine fibroids in women
3-AMINO-6-METHOXYPYRIDAZINE	1.00

General information

Strengthening regulatory framework, India to join the global quality scheme.

India is to join an international system - the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (PIC/S) - that fosters cooperation between countries and regulatory authorities on good manufacturing practices (GMPs) to improve the quality of its medical products.

News here.

Manufacturing Technology Trends

How manufacturing technology shapes quality and compliance in equipment design.

The medical industry faces strict regulatory requirements. Meeting these standards requires close attention and thorough planning before the pharmaceutical equipment design phase. That can be difficult with conventional approaches, but new manufacturing technology can optimize the process.

News here

Intellectual Property 

The court’s decision favours Merck in Sugammadex and the complexity associated with Patent term extension.

Here is the press release from Merck.

Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. District Court for the District of New Jersey ruled in favour of the company and found that Merck correctly calculated the Patent Term Extension period for the primary patent related to BRIDION® (sugammadex). 

Patent Term Extension is designed to restore some of the patent life lost during the regulatory review process for new drugs. 

Today’s ruling from the U.S. District Court for the District of New Jersey arms and validates Merck’s U.S. patent protection for BRIDION through at least January 2026. “Merck’s science and technology was used to develop and launch BRIDION, and we’re pleased that the Court recognized the validity of our full patent extension period granted by the Patent Office,” said Jennifer Zachary, executive vice president and general counsel, Merck. “Innovations like these contribute to a broader ecosystem that allows us to continue investing in research and development to bring important new therapies and vaccines forward to the patients who need them.”

Today’s write-up for a change is not an analysis or commentary about of this case. We don’t have paid access to PACER, where we would get the court document quickly. However, let us understand how FDA determined the extension period in this case. Please note this article is being drafted on 17 June 2023, and by the time this article is published, there could be a possibility that this decision could be available in the public domain. 

So, now about Patent Term Extensions (PTE). The Drug Price Competition and Patent Term Restoration Act and the Generic Animal Drug and Patent Term Restoration Act generally provide that a patent may be extended for a period of up to 5 years so long as the patented item was subject to regulatory review by FDA before the item was marketed. 

Under these acts, a product’s regulatory review period forms the basis for determining the amount of extension an applicant may receive. 

A regulatory review period consists of two periods of time: A testing phase and an approval phase. 

For human drug products, the testing phase begins when the exemption to permit the clinical investigations of the drug becomes effective (broadly, one can consider this as IND filing date. This is an exemption to permit the clinical investigations of the drug and start of conducting clinical testing) and runs until the approval phase begins. 

Then the approval phase starts with the initial submission of an application to market the human drug product and continues (ie NDA submission) until FDA grants permission to market the drug product. 

Generally a portion of a regulatory review period may count toward the actual amount of extension. However,  the Director of USPTO may award FDA’s determination of the length of a regulatory review period for a human drug product and will include all of the testing phase and approval phase.

FDA approved for marketing of the human drug product BRIDION (sugammadex sodium) on 15 December 2015. BRIDION is indicated for the reversal of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide in adults undergoing surgery. 

Subsequent to this approval, the USPTO received a patent term restoration application for BRIDION (U.S. Patent No. RE44733) from Merck Sharp & Dohme, B.V., and the USPTO requested FDA’s assistance in determining this patent’s eligibility for patent term restoration. 

In a letter dated 23 September 2016, FDA advised the USPTO that this human drug product (ie BRIDION (sugammadex sodium) had undergone a regulatory review period and that the approval of BRIDION represented the first permitted commercial marketing or use of the product. Thereafter, the USPTO requested that FDA determine the product’s regulatory review period. 

Determination of Regulatory Review Period

These periods of time were derived from the following dates: 

1. IND date determined was 13 April 2004.  

2. FDA has verified the applicant’s claim that the new drug application (NDA) for BRIDION (NDA 022225) was initially submitted on October 31, 2007. 

3. The date the application was approved: 15 December 2015. FDA has verified the applicant’s claim that NDA 022225 was approved on 15 December 15 2015. This determination of the regulatory review period establishes the maximum potential length of a patent extension. 

4. For determination of the Regulatory Review Period FDA has determined that the applicable regulatory review period for BRIDION is 4,265 days. Of this time, 1,297 days occurred during the testing phase of the regulatory review period (ie broadly IND), while 2,968 days occurred during the approval phase (NDA). 

5. However, the USPTO applies several statutory limitations in its calculations of the actual period for patent extension. One of which is the maximum extension could be of 5 years. It comes to around 1,826 days. Hence, in its application for patent extension, the applicant (Merck) sought 1,826 days of patent term extension.

In the press release you read at the start of the article, the U.S. District Court for the District of New Jersey ruled in favour of Merck and found that Merck had correctly calculated the Patent Term Extension related to BRIDION and U.S. Patent No. RE44733.