API and IP Newsletter

Contents

Recent 505 (b) (2) filings.

General information

Pharmaceutical Drug Regulation and Mortality: Evidence from Electronic Cigarettes

First-in-Class Drugs Offered Greater Regulatory Flexibility in the US vs Europe

Intellectual Property

Roche vs Natco -Risdiplam -Delhi High Court

Recent 505 (b) (2) filings. 

We follow 505 (b) (2) filings every month. This write-up consists of 505 (b) (2) NDA approvals for March 2025. 

General information

Pharmaceutical Drug Regulation and Mortality: Evidence from Electronic Cigarettes

Exempting e cigarettes from FDA regulation reduced mortality attributable to smoking by approximately 10 percent

For comparison, a prior study found that a $1 increase in cigarette taxes experienced between the ages of 14 and 17 reduced mortality by 4 percent. Furthermore, our findings reveal that the regulation exemption reduced the causes of death most associated with smoking by the largest amount. 

News here

First-in-Class Drugs Offered Greater Regulatory Flexibility in the US vs Europe

Between 2013 and 2023, 81% of first-in-class drugs were approved under one of the FDA’s expedited programs.

First-in-class drugs are often considered a signifier of innovation in drug discovery; however, they can also carry substantial uncertainty. A new comparison of approval data for first-in-class drugs approved by the US Food and Drug Administration (FDA) and those approved by the European Medicines Agency (EMA) revealed that the FDA is more likely to offer regulatory flexibility and designate first-in-class drugs for expedited review. 

News here

Intellectual Property 

Roche vs Natco -Risdiplam -Delhi High Court

The present suit has been filed by Roche against Natco, alleging infringement of Patent No. IN 334397 (IN‟397-Suit Patent/Species Patent). Through this application, the patentee Roche seeks an interim injunction to restrain the Suit Patent's infringement, titled " COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY. “ 

This issue was presented before the Single Judge Bench of the Delhi High Court. 

The Suit Patent, which is a “Species Patent” inter alia for the product “Risdiplam, " pertains to compounds that target Survival Motor Neuron 2 ("SMN2") and are used in the treatment of Spinal Muscular Atrophy ("SMA"). The Suit Patent is issued to Roche. 

The Suit Patent has a term of 20 years, beginning on May 11, 2015, and expiring on May 11, 2035. No pre-grant opposition, post-grant opposition, or revocation proceedings have been filed against the Suit Patent in India.

The corresponding patents to the Suit Patent have been granted in about 60 countries worldwide.

Risdiplam is the active pharmaceutical ingredient ("API") in Roche’s commercial product, marketed under the brand name “ EVRYSDI® “ in various countries worldwide, including India. 

Risdiplam is an oral prescription medication approved for treating SMA in patients aged two months or older. SMA is a rare genetic neuromuscular disorder caused by a mutation in the Survival Motor Neuron 1 ("SMN1") gene, resulting in a deficiency of SMN protein. This deficiency affects motor nerve cells and diminishes the ability to walk, sit, eat, and breathe.

The patentee Roche discovered the listing of Risdiplam on the defendant Natco’s website under the APIs under the development section. Further investigation revealed that Natco was preparing to produce Risdiplam API commercially. Additionally, Natco was found to have filed a patent application numbered 202241055182 on 26 September 2022, titled' Improved Process for the Preparation of Risdiplam and its Intermediates' for manufacturing Risdiplam. Hence, the present suit has been filed by the plaintiff Roche, alleging infringement by Natco of their rights in the Suit Patent.

On behalf of the plaintiff Roche, the following submissions have been made:

1. The defendant, Natco, has admitted to infringement, as it acknowledges being in the process of launching Risdiplam. 
2. Natco’s entire case is based on WO‟916 (WO 2013/119916 A2) , which is the International Genus Patent related to the Suit Patent. 
3. Natco has based its entire case on statements made in other jurisdictions regarding the PTEs. However, none of Roche's statements overseas amount to an admission that WO‟916 specifically discloses Risdiplam.
4. The Suit Patent is an old patent filed in 2016, claiming priority since 2014. It remains valid and active, having been granted in 2020. Additionally, the corresponding patents related to the specific compound Risdiplam have been granted in over 60 countries, and none have been revoked or invalidated in any jurisdiction.
5. The granting of an INN indicates that it is a new chemical entity, as INN naming is only available for new compounds. The International Search Authority ("ISA") has determined the Suit Patent to be novel and non-obvious after considering WO‟916.
6. Natco has fundamentally based its entire case on statements made in other jurisdictions regarding the PTE. In its arguments, Natco did not reference the prior art document WO‟916 or the patent in question to assess patentability requirements. 
7. The Suit Patent enjoys a strong presumption of validity, and Natco  has clearly failed to establish any challenge to that validity. Given that the Suit Patent is prima facie valid and that infringement is admitted, Roche is entitled to an injunction against Natco. 
8. Roche has developed the only oral drug for SMA in the world. The costs associated with developing a new molecule, as Roche has done, are extremely high, while companies that produce generic versions, like Natco, incur minimal Research and Development (R&D) expenses. Therefore, a balance is necessary between the interests of the innovators and the generic medicines industry. 
9. Roche has voluntarily offered significant price reductions and discounts to the Government of India to support SMA patients in the country. 
10. Natco is a habitual infringer, with multiple lawsuits filed against them in which injunctions have been granted. They have also breached undertakings and paid damages in settlements. 
11. A Person of Ordinary Skill in the Art refers to a typical individual, not an expert, as Natco suggests. Tests for determining obviousness and insufficiency are evaluated from the viewpoint of A Person of Ordinary Skill in the Art, not from that of an expert. Therefore, Natco’s interpretation of A Person of Ordinary Skill in the Art is inaccurate. 
12. There has been no evergreening in this case. Evergreening does not pertain to new compounds, and it is evident that Risdiplam is a new compound.
13. Risdiplam cannot be anticipated or rendered obvious based on WO‟916. The International Genus Patent, WO‟916, does not specifically disclose Risdiplam, and there is no specific example of Risdiplam found in WO‟916. 
14. Without hindsight, a person of ordinary skill in the art cannot recognise that Risdiplam would be the product.
15. The lead candidate selected from WO‟916 was the compound RG7800, as disclosed within the document. However, RG7800 was later halted due to retinal toxicity, although it was reasonable for a person of ordinary skill in the art to choose RG7800 based on WO‟916. 
16. Therefore, comparing the structures of the failed compound, i.e., RG7800, with that of Risdiplam, one can easily see the difference in the same, hence demonstrating that Risdiplam was a new invention.
17. 17. There was no challenge regarding novelty or anticipation posed by the Indian Patent Office ("IPO") during the prosecution of the Suit Patent, even though the Patent Office examined WO'916. Furthermore, WO‟916 was mentioned in the description of the Suit Patent. Thus, both the IPO and the ISA, along with all authorities in over 60 jurisdictions where the Species Patent has been granted, were explicitly aware of the document in question. 
18. Thus, WO‟916 has been considered in multiple jurisdictions, and no jurisdiction viewed it as anticipating the Species Patent or Risdiplam. 
19. The Suit Patent is not obvious based on WO‟916, as claimed by Natco. At the priority date of the Suit Patent, a Person of Ordinary Skill in the Art would have no basis for selecting a particular compound, as claimed by Natco. There is no guidance for a Person of Ordinary Skill in the Art to narrow down to the compound of formula from various Markush Structures. 
20. Natco has miserably failed to provide reasons for A Person of Ordinary Skill in the Art to select and modify the compound and the multiple substituents to arrive at Risdiplam. 
21. Reliance on Roche’s statements in applications for PTEs is entirely misplaced and legally indefensible. Statements made during the prosecution of foreign applications are irrelevant, as they respond to unique patentability requirements abroad. 
22. The context in which statements for the grant of PTEs have been made is completely different and cannot be termed an admission on any account. Furthermore, if the statements made in other jurisdictions amounted to an admission of disclosure, the novelty would be destroyed in this country.

Submissions of Natco

1. Roche has engaged in evergreening and unlawful PTE in India by applying for a species patent instead of an Indian Genus counterpart to US‟955/WO‟916, which would have expired in 2033. By applying for a species patent in India, Roche has secured an unlawful PTE of two years because Risdiplam is not specifically disclosed by the International Genus Patent. However, it is admittedly covered by the same. Thus, this is a case of International Genus versus Indian Species.
2. Roche has attempted to shift the focus of the case from the issues of evergreening and patent validity to the value of the product, Risdiplam, and the labelling of Natco as a habitual infringer.  
3. An interim injunction cannot be granted merely upon request in alleged patent infringement cases. This principle applies with even greater strictness to cases involving pharmaceutical patents. The Patents Act does not confer presumptive validity to a patent, even if granted after an unsuccessful pre-grant opposition or endures a post-grant opposition. 
4. The price under Roche’s Patient Support Program in India is also unaffordable. Patients pay Rs. 12.5 lakhs for 2 bottles and receive 3 bottles free. Thus, patients get 5 bottles for Rs. 12.5 lakhs. For a patient weighing 20 kilograms (kgs) or more, who needs 30 bottles a year, the cost will still exceed Rs. 30 lakhs Lacs. 13.5 The high cost of the drug Risdiplam, the only approved drug in India, is leading to challenges in making it available and accessible to all patients diagnosed or undiagnosed with SMA in India.
5. The Government of India has launched the National Policy for Rare Diseases, 2021, aimed at treating patients with rare diseases. In this policy, rare diseases have been categorized. A provision for financial support of up to Rs. 50 lakhs for patients suffering from rare diseases has been introduced. However, considering the high cost of patented medicines such as Risdiplam, these government provisions will be inadequate unless generic competition is introduced to lower prices through local manufacturing.
6. Another important point highlighted during the arguments is the various statements made on behalf of Roche in foreign jurisdictions, where Roche has categorical admitted that the International Genus Patent not only covers the product Evrysdi, i.e., Risdiplam, but is also generically disclosed in the Genus Patent. 
7. On the one hand, Roche has argued that, despite the coverage of Risdiplam by the International Genus Patent, the product was first discovered and specifically disclosed only in the Species Patent. On the other hand, Roche has secured PTEs for Genus Patents in nearly every major jurisdiction, such as the US and Australia, based on express statements that Evrysdi, or Risdiplam, is the specific commercial product whose discovery and regulatory approval is directly traceable to the respective Genus Patents. The factual admissions made by Roche regarding the PTE applications for the Genus Patent in the US and Australia reveal the position taken by the patentee itself: that the discovery and development of Risdiplam can be traced back to the US Genus Patent, US‟955, and consequently the International Genus Patent, i.e WO‟916. 

Issue of Obviousness - Section 64 (1)(f) of the Patents Act:

1. The defendant, Natco, has also challenged the validity of the Suit Patent, which is a Species Patent, under Section 64(1)(f) of the Patents Act, on the grounds of obviousness. Specifically, Natco alleges that the compound in question, Risdiplam, is obvious to a person skilled in the art or one knowledgeable in the field, due to the International Genus Patent, WO‟916.
2. The Single Judge Bench of the Delhi High Court stated that, in previous cases, this Court has categorically held that when the inventor is the same, the tests of " obvious to a person skilled in the art" cannot be viewed in the context of a person ordinarily skilled in the art, but must be considered in the context of a person who is knowledgeable in the field 
3. This Court has noted that at least four inventors in the International Genus Patent, which Natco has cited as prior art, are also associated with the Suit Patent, a Species Patent. Therefore, in light of previous decisions, the test of obviousness in the present case should be evaluated from the perspective of a knowledgeable person.
4. Accordingly, the Court stated that the question before this Court is to determine whether the compound in question, Risdiplam, is obvious to a person skilled in the art or knowledgeable in the field, based on the cited prior art, specifically International Genus Patent, WO‟916.
5. This Court notes that Natco has relied upon Compound 809 in the complete specification of the International Genus Patent, WO‟916, as well as the chemical name of Compound 809 provided in the complete specification of the International Genus Patent Patent.
6. The primary distinction between Compound 809 in the International Genus Patent and Risdiplam in the Suit Patent is the presence of nitrogen (N) in Risdiplam. At the same time, compound 809 of the International Genus Patent features a carbon-hydrogen ("CH") group at the even position.

   

The opinion of the Court

1. The International Genus Patent discloses 835 compounds, among which Pyrimidine is a component in nearly all, including Compound 809. Additionally, Pyridine is also found in most of the compounds. According to scientific definitions, Pyridine contains one nitrogen atom, while Pyrimidine has two nitrogen atoms. Therefore, it is evident that the common component in most compounds disclosed in the International Genus Patent pertains to the nitrogen atom, which may be either Pyridine or Pyrimidine.
2. At this stage, it would be beneficial to refer to Natco's reply to the interim injunction application, which states clearly that the International Genus Patent discloses different chemical structures with nitrogen positioned at various locations. 
3. The court concluded that International Genus Patent WO 916 states that various fused-ring heterocycles containing nitrogen at different positions within the same ring could be used. Therefore, it is submitted that using the same type of ring while varying the number of nitrogen atoms and their positions is obvious to a person skilled in the art.
4. Therefore, the court stated that, given the numerous occurrences of the nitrogen atom in various compounds, it is established that it would have been obvious to a person skilled in the art or someone knowledgeable that nitrogen is a dominant component of most compounds disclosed in the International Genus Patent. Thus, such a person would easily have been motivated to use the nitrogen atom instead of the carbon atom while examining Compound 809 in the International Genus Patent. The defendant, Natco, has demonstrated that the compounds claimed in the Suit Patent represent routine optimisation of those disclosed in the prior art. Furthermore, this Court acknowledges Natco’s submission that it is common practice in the pharmaceutical field to make iterative modifications to chemical structures to enhance properties such as potency, selectivity, or metabolic stability. 
5. The Court further stated that Roche's misleading statements, despite being aware of compound 809 in WO 916 Patent- Roche’s own document- indicate that the Suit Patent was obtained through false suggestion.
6. Roche falsely claimed that the WO 916 Patent citation does not remotely disclose the compounds of claim 1 (Risdiplam) or other claims of the Suit patent. In fact, Roche has always known that WO 916 exemplified compound 809. 
7. The Government of India has expressed concern about the financial burden of providing economic aid for supplying drugs to patients suffering from rare diseases.
8. Roche is currently importing the drug into India, resulting in a prohibitively high cost for the medication. Clearly, Roche intends to profit from the drug. Therefore, Roche could be entitled to compensation in damages if they succeed at the end of the trial. Regarding the balance of convenience and irreparable damage, the other two essential tests that Roche must satisfy for granting an interim injunction, in the Judge’s opinion, have yet again failed.
9. Therefore, on 24 March, the Court decided the balance of convenience issue against Roche and issued an order in favour of Natco.   

Decision here

Interestingly, Roche has not validated the International Genus Patent related to the Suit Patent family WO2013119916 in India. If they had filed it in India, then they would have had compound protection until 2033. 

So, Roche must defend their specific compound patent (Species Patent) protected by IN 334397 in India. 

Roche appealed against a single judge’s order from 24 March that refused to stop Natco Pharma from manufacturing a generic version of Risdiplam.

News here

This article will be published on our website and LinkedIn page in the first week of April 2025, and there may be some developments in the case by then. We will continue to monitor this case and keep our readers informed.