In a major decision that is likely to impact evergreening of pharmaceutical patents in India, the Delhi High Court vacated interim injunctions granted to AstraZeneca, a big pharma multinational, against three generics manufacturers, Micro Labs, Natco Pharma, and Dr. Reddy’s Laboratories. The case involved allegations of infringement of AstraZeneca’s three patents, for offering a generic version of AstraZeneca’s drug-TICAGRELOR for sale under the brand name BRILINTA.
AstraZeneca has three Indian patents (IN ‘907, IN ‘984, IN ‘674) for Ticagrelor, a platelet inhibitor drug, which serves patients that recently suffered a heart attack. IN ‘907 covers TICAGRELOR by disclosing a number of compounds by Markush structure. It also claims TICAGRELOR specifically in an individualized form. IN’984 discloses a crystalline form of TICAGRELOR, and IN’674 covers the finished pharmaceutical formulation of TICAGRELOR.
The Delhi High Court had previously granted an interim injunction to AstraZeneca in the same matter. In early August, the question of a permanent injunction in the matter came up. The Delhi High Court, in its recent judgment dated August 8, 2019, dealt with injunction applications of AstraZeneca AB & ORS vs Micro Labs Ltd. (CS(COMM749/2018)); AstraZeneca AB & ANR vs Natco Pharma Ltd. (CS(COMM) 792/2018); and AstraZeneca AB & ANR vs Dr. Reddy’s laboratories limited, (CS(COMM) 1023/2018).
Challenging the validity of AstraZeneca’s patents, the defendants argued that the pharma major had deliberately suppressed information that its genus patent (IN’229) which covers and discloses TICAGRELOR was due to expire in July 2018. Critically, this genus patent was not a suit patent in the present case. The defendants argued that AstraZeneca was also commercializing TICAGRELOR through its genus patent, for which they relied upon working statements (Form 27) filed for the period of 2012-2018. They also referred to admissions made in AstraZeneca’s counterpart US application to show that TICAGRELOR was disclosed in the genus patent, and to make the case that this was a textbook example of evergreening.
Besides issues of improper disclosure, the defendants also challenged the validity of the suit patents. They pointed out that the suit patents lacked novelty by prior claiming (from IN’ 229), they were obvious, and not patentable under Section 3(d) of the Patents Act, 1970. They argued that there was nothing to show that TICAGRELOR was more efficacious as compared to the compounds disclosed and covered in the genus patent.They also alleged that there was a failure in disclosing the necessary information required under Section 8 of the Act.On its part, AstraZeneca argued that the genus patent just covered TICAGRELOR and did not disclose the drug. In order to destroy the novelty of a specific compound under prior claiming, it argued that the compound should be claimed in an individualized form. AstraZeneca pointed out that the genus patent was published after the filing date of the species patent IN’907, so it did not qualify as prior art. Regarding the working statements in Form 27, AstraZeneca’s stand was that the genus patent was worked through TICAGRELOR, but it did not mean that TICAGRELOR was disclosed therein. It argued that a person skilled in the art would find it difficult to isolate TICAGRELOR from a large number of compounds disclosed by the genus patent.
In response to allegations of evergreening, AstraZeneca argued that merely because the genus patent was structurally close to TICAGRELOR did not mean that TICAGRELOR was a derivative of known form. It also relied on the affidavit filed by an expert, Dr Robert Riley, who stated that the drug had a superior metabolic establishment and has lower dose predicament. AstraZeneca argued that the enhancement of therapeutic efficacy was evident from the expert’s evidence, and that TICAGRELOR did not fall under the exception of Section 3(d) of the Patents Act, 1970.
In respect of Form 27 and affirmations in the US, AstraZeneca argued that form 27 only stated that the genus patent had worked through TICAGRELOR. This did not mean that TICAGRELOR had been disclosed therein. Further, AstraZeneca’s affirmations and actions were consistent with the US Laws in the US proceedings. For section 8 requirement, AstraZeneca said there was substantial compliance of the statutory provisions and there was no mala fide suppression and hence section 8 of the Patent Act would have no application.
On the question of prior claiming, the Delhi High Court found it was a mixed question of law and fact, as an expert is required to decide whether TICAGRELOR was either covered or covered and disclosed in the now-expired genus patent. Regarding the applicability of Section 3(d), the Court noted that both the compounds, namely, equivalents of IN ‘229 and IN ‘907, could be used as pharmaceutical agents for “inhibition of platelet aggregation”. Thus, it concluded that the suit patents were not something altogether new or completely unfamiliar or unconnected to IN ‘229.
Regarding efficacy, the Court relied on the expert evidence for assessing therapeutic efficacy. Critically, it noted that there was no explanation from AstraZeneca as to how the stated advantage, namely, lower dose and increased metabolic stability, would amount to enhancement of therapeutic efficacy over IN ‘229.
The Court took a restrictive approach and relied on the Supreme Court’s decision in Novartis vs Union of India(Novartis Ag v. Union of India, (2013) 6 SCC 1), to hold that not all advantages or beneficial properties were relevant but only such properties were relevant that directly related to therapeutic efficacy. Thus, expert evidence was required to show TICAGRELOR differed significantly from the compounds disclosed in the genus patent in terms of efficacy.
Regarding section 8, the Court found that there was prima facie substantial compliance of statutory requirements of Section 8 of the Act. In fact, it was stated that the failure to mention the proceedings in some countries were not material enough to vacate the interim order.
Regarding affirmations in US litigation and Forms 27, the Court found that AstraZeneca had failed to explain the affirmations made in form 27 and litigation commenced in the USA against Mylan INC.
In sum, the Court found that the defendants had strong grounds to challenge the validity of the suit patents. Thus, prima facie case was not made out by AstraZeneca. Since the genus patent IN 229 had expired on 14 July 2018, balance of convenience was also in favor of the defendants.Thus, the Court vacated the interim order and allowed the defendants to sell the generic version of TICAGRELOR at a cheaper rate of Rs 20/- and asked them to maintain accounts.
For AstraZeneca, besides losing a key infringement suit and losing ground in the Indian market, this decision has also put the validity of its three suit patents under cloud. The fate of these patents will be decided in future hearings.
For innovator companies, generally, this decision is likely to impact strategies of evergreening patents: species patents for pharmaceutical drugs will now have to demonstrate an enhancement in therapeutic efficacy. This decision will most certainly demand that innovator companies rethink their filing strategies, as also strategies in filing working statements before the Indian Patent Office.