API and IP Newsletter

 

Contents

• Analysis of patent families filed by Glenmark in the recent past.

• General information

• FDA updates the list of off-patent drugs without an approved generic

• Sourav Ganguly and Anil Kumble partner with Mankind Pharma

• Intellectual Property

• Astellas lost the case for extended-release drug formulations of mirabegron.

Analysis of patent families filed by Glenmark in the recent past.

We analyse patent applications filed by leading pharmaceutical companies in India. This week we chose Glenmark. Glenmark filed about 40 PCT applications in the last 4 years. 

Some of our observations are as below.

Publication Number	Title - DWPI	Publication Date	SIDVIM comments
WO 2023047323A1	Preparation of amorphous omadacycline tosylate for treating adult patients with community-acquired bacterial pneumonia infection involves contacting omadacycline with a mixture of alcohol and ether, treating the mixture with p-toluene sulphonic acid monohydrate, and adding antisolvent to the mixture	2023-03-30	Omadacycline tosylate is approved in October 2018. It will enjoy GAIN exclusivity till October 2028. There is a crystalline form patent issued to the innovator, which would expire in September 2030. To file ANDA with a non-infringing argument, one would need circumvention of crystalline form patent. This application perhaps provides an advantage to Glenmark over the competition.
WO 2023031753A2	Treating moderate to severe chronic obstructive pulmonary disease in the subject by administering nebulization composition comprising tiotropium, where nebulization composition is administered once day to the subject and nebulization composition is administered via nebulizer	2023-03-09	Worldwide generic Tiotropium MDI market is about USD 2.5b. Tiotropium bromide monohydrate is approved in the U.S. under the brand name Spiriva Respimat® as an aqueous formulation for oral inhalation with a metered dose inhaler (MDI). The recommended dose of Spiriva Respimat® is two inhalations once daily for a total daily dose of 5 mcg of tiotropium daily. MDI device is complex and requires the patient to coordinate breathing with the device during the administration of medication. Nebulization formulation is convenient for COPD patients. This patent family by Glenmark addresses a need for improved methods of treating moderate to severe COPD using tiotropium bromide administered as a nebulization solution. Glenmark could be developing 505(b) (2) for tiotropium bromide employing nebulization.
WO 2023281417A1	New substituted pyrimidine compound used in a pharmaceutical composition for treating mitogen-activated protein kinase kinase kinase kinase 1-mediated disease, disorder, syndrome or condition, e.g. cancer including lung cancer, colon cancer and breast cancer	2023-01-12	This is a proprietary molecule of Glenmark. It is an inhibitor of MAP4K1. Several small molecule inhibitors of MAP4K1 have been reported, but they do not inhibit MAP4K1 selectively or even preferentially. Sunitinib inhibits MAP4K1 at nanomolar concentrations, but it is a broad-spectrum receptor tyrosine kinase inhibitor. The major challenge currently faced in the field is the lack of MAP4K1-specific inhibitors. This patent family allegedly provides novel, highly effective small-molecule inhibitors of MAP4K1 and addresses this challenge of specificity.
WO 2023017393A1	Preparing olaparib, used to treat cancer by e.g. reacting 2-fluoro-5-formylbenzoic acid with cyclopropyl(piperazin-1-yl)methanone in the presence of coupling agent to 3-((4-(cyclopropylcarbonyl)piperazin-1-yl)carbonyl)-4-fluoro benzaldehyde	2023-02-16	Olaparib is a 2004 molecule, several processes are reported, and many polymorphs are known.   The present invention also provides an efficient process for the preparation of crystalline Form G1 of Olaparib.
WO 2022263935A1	Composition used to treat diabetes mellitus, impaired glucose tolerance, insulin resistance, and diabetic complication e.g. hyperglycemia, comprises remogliflozin etabonate, metformin hydrochloride, vildagliptin, and excipient	2022-12-22	Remogliflozin was commercially launched first in India by Glenmark in May 2019. The combination contains Remogliflozin (100 mg) + Vildagliptin (50 mg) + Metformin (500/1000 mg) in a fixed dose and twice daily. The product is not launched by GSK in many countries. They stopped working on it.  This patent family relates to FDCs. None of the prior arts discloses a combination of Remogliflozin, Vildagliptin and Metformin. Further, the prior art doesn’t disclose a bilayer tablet comprising the first layer of Remogliflozin and Metformin and a second layer of Vildagliptin. This invention could be useful for domestic markets and some Less Regulated markets.

General information

FDA updates list of off-patent drugs without an approved generic

Today, the US Food and Drug Administration published an update to the “List of Off-Patent, Off-Exclusivity Drugs without an Approved Generic” (OPOE list).

News here.

Sourav Ganguly and Anil Kumble partner with Mankind Pharma

Mankind Pharma has launched a new range of medicines that will boast the same level of Active Pharmaceutical Ingredient (API) quality in the Drug Master File (DMF) of the APIs submitted to the FDA. To promote and generate awareness about these medicines, the pharma giant has partnered with cricket legends Sourav Ganguly and Anil Kumble & launched a comprehensive 360-degree marketing campaign.

News here

Intellectual Property 

Astellas lost the case for extended-release drug formulations of mirabegron.

Astellas Pharma Inc. confirmed the U.S. District Court for the District of Delaware issued a decision on 09 June 2023 finding U.S. Patent No. 10,842,780 (the “’780 Patent”, which expires in March 2030) invalid. 

The ‘780 Patent covers extended-release drug formulations of mirabegron, including Myrbetriq®. This lawsuit was filed by Astellas in the U.S. District Court for the District of Delaware, requesting a judgement that certain generic pharmaceutical companies’ proposed generic versions of Myrbetriq® infringe the ’780 Patent. 

Astellas plans to appeal the decision to the United States Court of Appeals for the Federal Circuit (CAFC).

The claim of US 10842780 is as follows:

1. A pharmaceutical composition comprising 10 mg to 200 mg of mirabegron  or a pharmaceutically acceptable salt thereof, in a sustained release hydrogel-forming formulation comprising a hydrogel-forming polymer having an average molecular weight of 100,000 to 8,000,000 and an additive having a water solubility of at least 0.1 g/mL at 20±5° C.,

wherein the hydrogel-forming polymer is at least one compound selected from the group consisting of polyethylene oxide, hydroxypropyl methylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, hydroxyethyl cellulose, and a carboxyvinyl polymer,

wherein the additive is at least one selected from the group consisting of polyethylene glycol, polyvinylpyrrolidone, D-mannitol, D-sorbitol, xylitol, lactose, sucrose, anhydrous maltose, D-fructose, dextran, glucose, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polyoxyethylene sorbitan higher fatty acid ester, sodium chloride, magnesium chloride, citric acid, tartaric acid, glycine, (3-alanine, lysine hydrochloride, and meglumine, and

wherein a drug dissolution rate from the pharmaceutical composition is 39% or less after 1.5 hours, and at least 75% after 7 hours, as measured in accordance with United States Pharmacopoeia in 900 mL of a USP buffer having a pH of 6.8 at a paddle rotation speed of 200 rpm.

This decision is not yet available at Court’s website.

We do not have access to a paid subscription to PACER and hence were curious about what is happening to the equivalent EP patent and at EPO. We checked EP 3827826. This divisional patent is not yet granted by EPO. Patentee Astellas is struggling at EPO too to seek grants of similar claims as that of the US, we noticed US claims are much narrower than the EP counterpart.

Following documents cited by EPO as prior art

D1: EP1440969 (YAMANOUCHI PHARMA CO LTD (JPI) 28 July 2004 (2004-07-28)

D2: EP1028111 (YAMANOUCHI PHARMA CO LTD [JPI) 16 August 2000 (2000-08-16)

D3: WO2004041276 (YAMANOUCHI PHARMACEUTICAL CO., LTD.) 21 May 2004 (2004-05-21)

D4: WO9406414 (YAMANOUCHI PHARMACEUTICAL CO., LTD.) 31 March 1994 (1994-03-31)

D5: JP2005519884T (ALZA CORP.) 7 July 2005 (2005-07 -07)

D6: JP2005162737 (ASTELLAS PHARMA INC.) 23 June 2005 (2005-06-23)

D7: WO2008084698 (ASTELLAS PHARMA INC.) 17 July 2008 (2008-07-17)

We will study inventive arguments being discussed at European Patent Office (EPO) in the search opinion.

Document D4 is considered as the closest prior art by the EPO

The claims disclose a sustained release preparation comprising a drug, an additive that ensures penetration of water into the core of the preparation in an amount of 5 to 60% by weight relative to the overall preparation and a hydrogel-forming polymer in an amount of 15 to 90% by weight relative to the overall preparation. 

D4 also teaches that the drug is not particularly limited as long as the drug is one intended for sustained release, D4 discloses the use of poly(ethylene glycol), poly(vinyl pyrrolidone) and the like as the additive, which ensures penetration of water into the core of the preparation, D4 also discloses use of polyethene oxide having a molecular weight of 2 million or higher as the hydrogel-forming polymer, and indicates that it is possible to add yellow iron sesquioxide or iron sesquioxide or a preservative and the like to the preparation. So, all essential features of impugned inventions are taught by D4.

Therefore, appropriately adjusting the release properties of a drug is a matter that persons skilled in the art routinely carry out by employing the known additives.

Documents D1 and D2 which are directed to drug formulations of Mirabregon, teach the addition of further compounds such as additives and hydrogel-forming polymers into the anti-obesity, anti-hyperlipemia formulations of this API. See in particular the §§ 14-15 in D1 and §§ 1-10 in D2.

There could be similar arguments in the U.S. District Court for the District of Delaware. We will post it as soon as docket is available in public domain. 

As per press release of Astellas patents covering crystal forms and methods of using mirabegron, which were the subject of earlier litigation, remain valid and expire in May 2024. Astellas does not anticipate the immediate launch of generic mirabegron. This decision will have no impact on the financial forecasts of the current fiscal year ending 31 March 2024.

Press release here