Background:
In India, patent applications filed for new forms of known chemical entities have always faced strict scrutiny under the provisions of Section 3(d) of the Indian Patents Act, 1970 (‘Act’). The judgement delivered by the Divisional Bench of the Delhi High Court presided by two justices, Hon’ble Justice Vibhu Bakhru and Hon’ble Justice Amit Mahajan on 24 April 2024, provided critical interpretations for some of the most disputed matters concerning the field of patenting new chemical entities (NCEs) and its forms, such as salts. The judgment which was issued in the case of Natco Pharma v. Novartis Ag and Anr.[1] reasserted the landmark decision that was made in the matter of Novartis v. UoI[2]. This case revolved around the interpretation of ‘enhanced efficacy’ under Section 3(d) of the Act. The Divisional Bench’s decision focused on following two pivotal issues under a broader question of a credible challenge to the validity of a patent:
1. Whether the enhanced bioavailability data could be construed as proof of enhanced ‘therapeutic efficacy’.
2. The concept of ‘Coverage v. Disclosure’ in patent applications.
Facts of the case:
1 Patent IN213176 (IN’176) owned by Novartis
Referred to as the first patent, IN’176 covers the base compound, i.e., Eltrombopag (ELT). This patent expired on May 24, 2021.
2. Patent IN 233161 (IN’161) owned by Novartis
Referred to as the suit patent, IN’161 claims a specific salt form of Eltrombopag, i.e., Eltrombopag-Olamine (ELT-O). This patent was to expire on May 21, 2023.
At the expiry of the first patent IN’ 176, Natco (Appellant) launched a drug containing ELT-O under the brand name Trombopag. Since ELT-O was the subject matter of an active Patent, i.e., IN’ 161 owned by Novartis (Respondents), the latter filed a suit seeking a decree of permanent injunction in June 2021 before the Single Bench of the Delhi High Court.
Natco in its defence alleged that IN’161 is invalid on the account of being a new form of known substance under Section 3(d) of the Act and that it is an attempt to ‘evergreen’ the patent on ELT by extending the monopoly beyond the expiration of IN’176. Natco also asserted that the patent ought to be revoked since ELT-O was already covered in the first patent IN’176.
Novartis in response stated that ELT-O provided enhanced solubility and bioavailability which led to enhanced therapeutic efficacy of the ELT-O when compared to the base compound, i.e., ELT. Also, ELT-O was only covered and never claimed in IN’ 176.
The Single Bench allowed an interim relief that restrained Natco from dealing in any manner in ELT-O either separately or in combination with any other compound. Primarily, the Single Bench held that (1) ELT-O was only covered and not disclosed in IN’176 and (2) the enhanced solubility and bioavailability of ELT-O leading to therapeutic efficacy can be used to overcome the barrier of Section 3(d) of the Act.
Natco then approached the aforesaid Divisional Bench with the plea of overturning the judgement delivered by the Single Judge.
Divisional Bench’s interpretation of Section 3(d) of the Act:
The main question that the Divisional Bench had to decide on was whether the enhanced solubility and bioavailability of ELT could be construed as enhanced therapeutic efficacy or if they were only a means of overcoming/reducing the negative impact of its poor solubility, because of which it cannot be formulated into pharmaceutical dosage forms.
Understanding of Section 3(d) of the Act:
Section 3(d) of the Act bars the patenting of ‘the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant.
Explanation. —For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.’
In its Judgement, the Court first explained the reason for the inclusion of the first part of Section 3(d) of the Act along with the explanation in Patents (Amendment) Act, 2005, for which the Court referred to Supreme Court’s order in Novartis supra and iterated that the Explanation to Section 3(d) of the Act amply sets out what are not considered as inventions. Although the legislature has excluded the incremental inventions from the Explanation substances, which differ significantly in their properties with regard to efficacy (therapeutic efficacy in pharmaceutical/chemical products), however, the statute clearly states that the aforementioned forms would be considered the same substance. The Court asserted that the rationale for excluding the specified forms of known substances was to exclude the ‘evergreening’ of the patents in respect of pharmaceutical/chemical substances.
Understanding of Enhancement of Known Efficacy:
Further, the Court focused on clarifying the term ‘enhanced efficacy’ within the framework of Section 3(d) of the Act. The Court specifically addressed whether data pertaining to enhanced bioavailability could satisfy the requirements of enhanced ‘therapeutic efficacy’.
The Court highlighted a clear distinction between bioavailability and therapeutic efficacy:
Bioavailability v. Therapeutic efficacy:
The Court referred to H.L. Sharma & K.K. Sharma, Principles of Pharmacology[3] in order to comprehend the term bioavailability used in the field of pharmacology. The Court observed that properties such as greater bioavailability, solubility, stability, and hygroscopicity are usual properties of the given forms of a substance.
Further, the Court referred to the Supreme Court’s order in Novartis supra, wherein a similar question was addressed, and it was contended on behalf of certain objectors that a demonstration of increased bioavailability is not a demonstration of enhanced efficacy.
The Supreme Court in Novartis supra held that ‘in whatever way therapeutic efficacy may be interpreted, this much is absolutely clear: that the physicochemical properties of the beta crystalline form of Imatinib Mesylate, namely, (i) more beneficial flow properties, (ii) better thermodynamic stability, and (iii) lower hygroscopicity, may be otherwise beneficial but these properties cannot even be taken into account for the purpose of the test of Section 3(d) of the Act, since these properties have nothing to do with therapeutic efficacy. …However, a determination that a drug product is bio-available is not in itself a determination of effectiveness.’
Thus, considering the above points, the Divisional Bench in the present matter concluded that solubility is a physico-chemical property and not a property of therapeutic efficacy. Also, that bioavailability is one of the pharmacokinetic parameters and not a direct measure of therapeutic efficacy. The Court went on to stress that improved bioavailability does not equate to increased therapeutic efficacy.
Divisional Bench’s interpretation on the concept of ‘Coverage v. Disclosure’ in patent applications:
To understand the concept of Coverage v. Disclosure, the Divisional Bench again relied on the Supreme Court’s order in Novartis (Supra) and held that there is no dichotomy between coverage and disclosure.
The Court held that the protection in respect of the said claim would extend to substances disclosed as well as to those that are not specifically disclosed but are obvious to a person skilled in art and/or can be anticipated.
The Court further held that ‘The gap between coverage and disclosure would thus, necessarily have to be confined to only those substances which are otherwise anticipated or obvious to a person skilled in the art. It cannot extend to other substances or products that are neither disclosed nor are obvious to or anticipated by a person skilled in the art.’
Conclusion
This ruling following the judicial precedent from the Honorable Supreme Court’s stance in the matter of Novartis reiterated that increased bioavailability is not a direct measure of enhanced efficacy. This indicates that for a new form of known substance, one must demonstrate enhanced therapeutic efficacy over the known substance, which cannot be solely based on the bioavailability data of the new form. The Divisional Bench further relied on the orders in the matters of Merck Sharp & Dohme Corporation & Anr. v. Glenmark Pharmaceuticals Ltd[4]. and Astrazeneca Ab & Anr. v. Intas Pharmaceuticals Ltd. Intas[5] for this ruling.
The present judgment resets the high bar for the pharmaceutical companies and reminds them of the intricacies of the provision of Section 3(d) of the Act which is exclusive to the Patents Act in India. Additionally, this ruling clarifies that the protection under Section 48 of the Act will also extend to those substances that are not specifically disclosed but are obvious to a person skilled in art and/or can be anticipated.
[The authors are Executive Director, Senior Associate and Senior Patent Analyst, respectively, in IPR practice at Lakshmikumaran & Sridharan Attorneys]
[1] Natco Pharma v. Novartis Ag and Anr
[3] H.L. Shama & K.K. Sharma, Principles of Pharmacology 32-32 (Paras Medical Publisher 3d ed. 2018)
[4] Merck Sharp & Dohme Corporation & Anr. vs Glenmark Pharmaceuticals Ltd
[5] Astrazeneca Ab & Anr. vs Intas Pharmaceuticals Ltd. Intas
