API and IP Newsletter

 Contents

• DMF filings by Indian companies

• General information

• Centre sets deadline for pharmaceutical firms to adopt WHO’s good manufacturing practices

• US Regulatory Risks, Litigation Likely To Slow FY24 Growth For India’s Top Pharma Firms, Says ICRA

• Intellectual Property

• T 3201/19 16-05-2023

DMF filings by Indian companies

We analyze DMF filings by Indian companies. FDA recently published quarterly DMF filing list. This week we analyzed DMFs filed in the month of April 2023. Some of our comments are as below. 

HOLDER	SUBJECT	Sidvim comments
MALLADI DRUGS AND PHARMACEUTICALS LTD	RITALINIC ACID	There are other 5 DMFs active. This is about 70-100 MT volume. Controlled substance handling is involved and there would be limited competition. Ritanilic acid has 4 isomers and yields would go down substantially while conversion to methylphenidate. Market for ADHD is shifting to Shire Mydayis since 2017 from Ritalin. This could have impact on Gx supply and intermediate ritalinic acid.
GLOBAL CALCIUM PRIVATE LTD	SELENIOUS ACID USP	Selenious acid is approved by FDA in Aril 2019. NCE-1 date will be in April 2024. There are already 5 DMFs filed. Selenious Acid Injection is approved for use in the paediatric population, including neonates, as a source of selenium for PN when oral or enteral nutrition is not possible, insufficient, or contraindicated. There are many other non-medical uses, such as preservative for Vit E.
AMI LIFESCIENCES PRIVATE LTD	ESLICARBAZEPINE ACETATE	Eslicarbazepine is anticonvulsants drug. More than one dozen active DMFs. DRL perhaps will enjoy first to file status and will share 180 Days exclusivity. Ami’s DMF is one among many.
HETERO DRUGS LTD	SOLRIAMFETOL HYDROCHLORIDE	Solriamfetol is used to treat excessive daytime sleepiness caused by narcolepsy. NCE-1 date was in June 2023. There are already 6 DMFs filed. No information about P-IV filings yet by any generic as per FDA website and it would be safe to guess NCE-1 date would be still open.
MAITHRI DRUGS PRIVATE LTD	VONOPRAZAN FUMARATE	Vonoprazan is in a class of medications called potassium-competitive acid blockers (PCAB). It was approved in the Japanese market in February 2015 and in Russia in April 2021. Five other DMFs filed. As per Orange book both combination products of Vonoprazan approved in May 2022 are discontinued! Reasons to be investigated further.

General information

Centre sets deadline for pharmaceutical firms to adopt WHO’s good manufacturing practices

The health ministry said that companies with turnover of over Rs 250 crore will have to implement the guidelines within six months.

News here.

US Regulatory Risks, Litigation Likely To Slow FY24 Growth For India’s Top Pharma Firms, Says ICRA

Executive Summary

The damage at one of Pfizer’s largest injectables facilities could lead to gains for a few Indian companies, analysts feel. However, regulatory risks, litigation pay-outs and other challenges will slow growth for domestic firms and Indian units of multinationals like Abbott and Pfizer in FY24, says rating agency ICRA as Q1 results begin coming in

News here

Intellectual Property 

T 3201/19 16-05-2023

This week, let us analyse inventive step arguments in polymer case at Board of Appeals at EPO.

There were six auxiliary requests (AR) filed and there were subtle differences in claims of each AR. Let us not get into all those complications and see how invective step was analysed by the appeal board for Claim 1 and 6 which were finally debated in depth during the proceedings.

EP 2855537 was issued to Borealis AG. It was opposed by The Dow Chemical Company. At first instance, patent was maintained in the amended form and matter was in appeal. 

The claims discussed are as below. 

"1. A low density polyethylene having a melt flow rate (MFR) according to ISO 1133 (190°C, 2.16 kg) which is at least 4.4 g/10 min, a storage modulus G', measured at a loss modulus G" of 5 kPa, which is above 3000 Pa and a vinylidene content which is at least 24/100k C.

"6. A process for production of a low density polyethylene having a melt flow rate (MFR) according to ISO 1133 (190°C, 2.16 kg) which is at least 4.4 g/10 min, a storage modulus G', measured at a loss modulus G" of 5 kPa, which is above 3000 Pa and a vinylidene content which is at least 24/100k C, in a tubular reactor by radical initiated polymerization under high pressure where the polymerization is performed by reacting a reaction mixture, comprising ethylene monomers, under action of one or more radical initiators, such as peroxides, oxygen or combinations thereof, wherein the amount of used radical initiators, i.e. the amount of used active oxygen, is at least 5 times the conventionally used amount, and, optionally, wherein inlet temperature of the reaction mixture into the first reaction zone of the reactor is 135 °C or lower, or, alternatively, from 120 to 135 °C."

Many documents cited as prior art. We will cover only those which would be relevant for this obviousness (inventive step) discussion. 

D8 is an experimental report in which, the parameters defined in operative claim 6 were measured on a sample of NUC 8007 between 25 April and 10 May 2012. 

According to this report, resin NUC 8007 meets the parametric requirements of the LDPE obtainable by the method of operative claim 6, i.e. the LDPE defined in granted claim 1.

There is discussion about Objective Technical Problem solved by the invention. It was concluded that the problem successfully solved by the subject-matter of claim 6 over the closest prior art can only reside in the provision of a process leading to the preparation of resin NUC 8007 or a further LDPE resin suitable for extrusion coating.

It was to be decided that whether the skilled person desiring to solve the problem identified above would, starting from the method of producing NUC 8007 as described in D4 (Plastic Film - Resin Material Guidebook 2004, Converting Technical Institute 2003, ISBN4-906451-30-6 C3068; pages 272-275 and translation thereof in English (D4a)), have modified the method for preparing NUC 8007 in such a way as to arrive at the subject matter of operative claim 6.

The skilled person knows how to produce by high pressure polymerization of ethylene in a tubular reactor the LDPE resin NUC 8007, i.e. a resin which satisfies the parametric requirements defined in operative claim 6. 

This process is undisputedly known to the skilled person to conventionally require the use of one or more radical initiators, such as peroxides, i.e. active oxygen. 

This is a fortiori also valid for the production in a tubular reactor of a LDPE resin which is not exactly NUC 8007, but a similar resin also encompassed by the parametric definition of operative claim 6. 

The only remaining question to be answered is whether the amount of active oxygen the skilled person would find obvious to use to prepare LDPE resin NUC 8007 or a similar resin can be qualified as at least 5 times the "conventionally used amount".

The expression "conventionally used amount" in operative claim 6 refers to a broad range of values which depends on a large number of variables, such as the polymer grade to be produced, the reactor set up, the type of initiators, the pressure and the temperature at which the reactor is operated. 

Moreover, the quantity of active oxygen defined as the "conventionally used amount" does not necessarily refer to one that could be used for the preparation of NUC 8007, since the polymer grade to which that amount refers is not specified in operative claim 6.

D10 (D. Kalyon et al., High Pressure Polymerization of Ethylene and Rheological Behavior of Polyethylene Product, Polymer Engineering and Science, May 1994, Vol. 34, No. 10, pages 804-814) already illustrates with the results shown in table 9 (page 810) that initiator amounts can be varied by a factor of at least 5 when preparing LDPE resins. 

The Board is convinced that the amount of active oxygen can be even more broadly varied when selecting as reference for the "conventional used amount" the preparation of a different LDPE resin, using a different reactor set, different initiators and/or different conditions for operating the reactor.

In these circumstances, and having regard to the vague and therefore broad definition of the feature "conventional used amount", it is concluded that the skilled person wishing to provide a method of producing resin NUC 8007 or a further LDPE resin suitable for extrusion coating would find it obvious to use an amount of active oxygen corresponding to at least five times this vaguely defined amount, and would thus arrive in an obvious manner at a method falling within the ambit of operative claim 6.

The Board opined that main request is therefore not allowable, as the subject-matter of its claim 6 does not involve an inventive step.

Decision here