AstraZeneca AB Vs. Intas Pharmaceuticals Limited

Species patents following a Markush patent must demonstrate a distinct inventive step

Introduction

The AstraZeneca AB & Anr. Vs. Intas Pharmaceuticals Limited case, decided on July 20, 2021, by the High Court of Delhi, represents a pivotal moment in Indian patent jurisprudence, particularly in the pharmaceutical sector. This dispute centered on the validity and infringement of patents covering Dapagliflozin (DAPA), a critical drug for managing type-II diabetes mellitus. AstraZeneca, a global pharmaceutical leader, sought to protect its intellectual property rights against multiple Indian generic drug manufacturers, including Intas Pharmaceuticals, Alkem Laboratories, and others. At the heart of the case was the interplay between two patents—a genus patent (IN 147) employing a Markush structure and a species patent (IN 625)—and whether DAPA was disclosed in the earlier patent, thereby challenging the validity of the later patent and AstraZeneca’s claim for interim injunctive relief. This case study provides an in-depth exploration of the factual and procedural background, the legal issues, the role of Markush patents, the submissions of the parties, the judicial reasoning, and the broader implications for patent law in India.

Detailed Factual Background

AstraZeneca AB, a Swedish entity, and its Indian subsidiary, AstraZeneca Pharma India Ltd., held two Indian patents: Indian Patent No. 205147 (IN 147), a genus patent granted on March 15, 2007, with an expiry date of October 2, 2020, and Indian Patent No. 235625 (IN 625), a species patent granted on July 9, 2009, with an expiry date of May 15, 2023. Both patents were originally granted to Bristol Myers Squibb Company and assigned to AstraZeneca AB via an Assignment Deed dated February 1, 2014. IN 147 was characterized as a Markush patent, covering a broad class of C-aryl glucosides that inhibit sodium-dependent glucose transporters (SGLT2), used to treat type-II diabetes and related conditions. This patent disclosed a Markush structure, a chemical formula representing a group of related compounds with permutations potentially encompassing millions of structurally diverse molecules, though only 80 compounds were specifically exemplified. IN 625, conversely, specifically claimed DAPA, a single molecule identified as a highly effective SGLT2 inhibitor.

AstraZeneca alleged that several Indian pharmaceutical companies, including Intas Pharmaceuticals, Alkem Laboratories, Zydus Healthcare, Eris Lifesciences, USV Pvt. Ltd., Torrent Pharmaceuticals, MSN Laboratories, Micro Labs, and Ajanta Pharma, were manufacturing and selling generic DAPA-based drugs, infringing both IN 147 and IN 625. The plaintiffs argued that while DAPA fell within the scope of IN 147’s Markush structure, it was not disclosed therein and was only specifically disclosed in IN 625, resulting from further research. They claimed DAPA was a novel, non-obvious invention, with IN 625 enjoying a presumption of validity, having been granted in over 70 countries and unchallenged in India until 2020.

The defendants countered that DAPA was disclosed in IN 147, rendering IN 625 invalid due to prior claiming, anticipation, and lack of inventive step. They highlighted AstraZeneca’s admissions in US proceedings, including before the US Patent and Trademark Office (USPTO) and in a Delaware lawsuit, where the company acknowledged DAPA’s coverage under the patent equivalent to IN 147. The defendants also alleged that AstraZeneca violated Section 8 of the Patents Act, 1970, by failing to disclose USPTO examination details and argued that the significant price difference between their generics and AstraZeneca’s branded drug justified denying interim relief in the public interest.

Understanding Markush Patents

A Markush patent, named after Eugene A. Markush, who pioneered this claim structure in the 1920s, is a specialized form of patent claim used primarily in chemistry and pharmaceuticals to cover a genus of compounds. The term originates from the US case Ex parte Markush, 1925 CD 126 (Com.Pat. 1924), where Assistant Commissioner Kinnan approved a claim format that enumerated alternative species within a genus, allowing a patent drafter to condense multiple dependent claims into a single claim. The court in the present case referenced In Re: Harnisch, 631 F.2d 716 (US Court of Customs and Patent Appeals, 1980), which clarified that a Markush claim is a type of definition by enumeration, not a novel invention but a drafting technique to broadly claim a group of related chemical compounds.

In a Markush claim, a general chemical structure is defined with variable substituents (e.g., “R” groups) that can be selected from a specified list, such as alkyls, halogens, or other functional groups. For example, a claim might state: “A compound of formula X, wherein R1 is selected from methyl, ethyl, or propyl, and R2 is selected from chlorine or bromine.” This structure allows the patentee to claim a vast number of compounds without listing each one, covering permutations that may run into millions, as in IN 147. The Harnisch case emphasized that Markush claims are not inherently “alternative” but are a legitimate way to claim a genus, provided the specification enables a person skilled in the art to practice the invention across the claimed scope.

In the context of Indian patent law, Markush claims are permissible under Section 10(5) of the Patents Act, 1970, which allows claims to relate to a single invention or a group of inventions linked by a single inventive concept. The court noted that IN 147’s Markush structure disclosed a core structure with multiple variables, exemplified by 80 compounds, but did not specifically name DAPA. AstraZeneca argued that this broad coverage did not constitute disclosure, as DAPA required further research to identify. The defendants, however, contended that coverage implied disclosure, particularly given AstraZeneca’s infringement claims for IN 147, relying on Novartis AG v. Union of India, (2013) 6 SCC 1, which suggested that compounds covered by a genus patent are known therefrom.

The significance of Markush patents in this case lies in their dual role: they enable broad protection for a class of compounds, potentially blocking competitors, but also pose challenges in establishing novelty and non-obviousness for subsequent species patents like IN 625. The court grappled with whether IN 147’s Markush claim disclosed DAPA sufficiently to invalidate IN 625 or whether DAPA’s specific disclosure in IN 625 constituted a distinct inventive step.

Detailed Procedural Background

AstraZeneca filed multiple suits in the High Court of Delhi under the Commercial Courts Act, 2015, seeking permanent injunctions to restrain the defendants from manufacturing and selling DAPA-based drugs. These suits included applications for interim injunctions. The suits were bifurcated into two sets: the first, against Intas Pharmaceuticals (CS(COMM) No.410/2020) and Alkem Laboratories (CS(COMM) No.411/2020), culminated in a common order on November 2, 2020, denying interim relief. The second set, against Torrent Pharmaceuticals, Micro Labs, Zydus Healthcare, Eris Lifesciences, USV Pvt. Ltd., MSN Laboratories, and Ajanta Pharma, resulted in a common order on November 18, 2020, also denying interim relief.

AstraZeneca appealed these orders, filing nine appeals under Section 13(1A) of the Commercial Courts Act, 2015, read with Order XLIII Rule 1(r) of the Code of Civil Procedure, 1908. The appeals, numbered FAO(OS)(COMM) 139/2020 to 161/2020, included applications for additional documents, stay, and interventions by third parties such as Natco Pharma and Shiv Shivam Pharma. The Division Bench, comprising Justice Rajiv Sahai Endlaw and Justice Amit Bansal, heard the appeals collectively via video conferencing from February 25, 2021, to May 28, 2021, reserving judgment on May 28, 2021, and delivering the final decision on July 20, 2021.

Issues Involved in the Case

The case raised several critical legal issues:

1. Disclosure of DAPA in IN 147’s Markush Structure: Whether DAPA, covered by IN 147’s Markush claim, was disclosed therein, either in law or fact, and whether such disclosure invalidated IN 625?
2. Validity of IN 625: Whether IN 625 was vulnerable to challenge on grounds of prior claiming, anticipation, lack of inventive step, or non-compliance with Section 8 of the Patents Act, 1970?
3. Infringement of Dual Patents: Whether the defendants’ manufacture and sale of DAPA infringed both IN 147 and IN 625, given AstraZeneca’s claim of infringement for both patents?
4. Entitlement to Interim Injunction: Whether AstraZeneca established a prima facie case, balance of convenience, and irreparable loss to warrant interim injunctive relief, considering the defendants’ credible challenge to IN 625’s validity?
5. Public Interest and Pricing: Whether the significant price difference between AstraZeneca’s branded drug and the defendants’ generics, coupled with the public health context of the COVID-19 pandemic, justified denying interim relief?

AstraZeneca’s Submissions

AstraZeneca argued that IN 147’s Markush structure, while covering DAPA within its broad scope, did not disclose it specifically. They emphasized that IN 147, granted in 2007 with a priority date of August 12, 1999, disclosed a core structure with millions of possible compounds, exemplified by 80 compounds, none of which were DAPA. DAPA was invented in 2001 and patented in IN 625, granted in 2009 with a priority date of May 20, 2002, following further research to identify the optimal SGLT2 inhibitor. AstraZeneca contended that DAPA was not obvious from IN 147, as the Markush structure provided no guidance on selecting DAPA, and any derivation relied on hindsight, which is impermissible under patent law (F. Hoffman-La Roche v. Cipla Ltd., 2015 (225) DLT 391).

The plaintiffs asserted that IN 625 enjoyed a presumption of validity, having been rigorously examined by the Indian Patent Office and granted in over 70 countries. They argued that the defendants’ 2020 challenges to IN 625 were mala fide, initiated as a counterblast to the infringement suits. On Section 8 compliance, AstraZeneca claimed they disclosed the US patent equivalent to IN 625 as a continuation-in-part of the US patent equivalent to IN 147, and the USPTO’s objection on obviousness-type double patenting was irrelevant, as it did not affect the Indian Patent Office’s assessment. They further argued that the balance of convenience favored them, as denial of interim relief would erode their market share and research investment, while the price difference (approximately Rs.1,100/month) was justified given their R&D costs.

Defendants’ Submissions

The defendants argued that DAPA was disclosed in IN 147’s Markush structure, as evidenced by AstraZeneca’s admissions in US proceedings. They noted that AstraZeneca agreed to align the validity period of the US patent equivalent to IN 625 with that of IN 147 before the USPTO and claimed infringement of the IN 147 equivalent in a Delaware lawsuit against Zydus Pharmaceuticals USA. Citing Novartis AG v. Union of India, (2013) 6 SCC 1, they argued that coverage in a genus patent implies disclosure, rendering IN 625 invalid for prior claiming and anticipation. They further contended that DAPA was obvious from IN 147’s example 12, which disclosed a methoxy-substituted compound close to DAPA’s ethoxy-substituted structure, as a skilled person could make the substitution (F. Hoffman-La Roche v. Cipla Ltd.).

The defendants alleged non-compliance with Section 8, claiming AstraZeneca concealed USPTO objections and their response, which admitted DAPA’s disclosure in the IN 147 equivalent. On interim relief, they argued that their credible challenge to IN 625’s validity precluded an injunction. They emphasized the balance of convenience, noting their domestic manufacturing versus AstraZeneca’s imports, and the public interest, given their generics’ lower prices (Rs.13.90–17.50 vs. Rs.54.40–57.29 per dose). They highlighted the need for affordable diabetes drugs during the COVID-19 pandemic, where diabetic patients faced heightened risks.

Detailed Discussion on Judgments Cited

The parties and the court referenced several judgments, each providing context to the Markush patent and other issues:

1. Novartis AG v. Union of India, (2013) 6 SCC 1: The defendants relied on this case to argue that there is no dichotomy between coverage and disclosure in a genus patent like IN 147’s Markush claim, suggesting DAPA’s coverage implied its disclosure. The Supreme Court in Novartis held that molecules covered by a genus patent are known therefrom, rejecting a strict separation of coverage and disclosure. However, the court in the present case noted that Novartis recognized a factual distinction, requiring case-specific analysis to determine whether IN 625’s specific disclosure of DAPA was distinct from IN 147’s Markush coverage.
2. F. Hoffman-La Roche v. Cipla Ltd., 2015 (225) DLT 391: Cited by the defendants to support their obviousness argument, this case held that prior art, even with multiple starting points, can suggest modifications to a skilled person. The court applied this to assess whether DAPA’s ethoxy substitution was obvious from IN 147’s methoxy-substituted example 12, impacting IN 625’s validity.
3. Wander Ltd. v. Antox India P. Ltd., 1990 Supp SCC 727: Referenced by the court to define the appellate review standard for interim injunctions, requiring perversity to warrant interference. The court used this to uphold both impugned orders denying relief, finding no perversity despite differing reasoning.
4. AZ Tech (India) v. Intex Technologies (India) Limited, Civil Appeal No.18892/2017 (Supreme Court, August 16, 2017): Cited by the court to critique exhaustive interim relief orders in IP cases, advocating for brevity. The court adhered to this by limiting its analysis and avoiding detailed discussion of all cited judgments.
5. In Re: Harnisch, 631 F.2d 716 (US Court of Customs and Patent Appeals, 1980): Referred to by the court to define Markush claims, explaining their origin as a drafting technique to enumerate species within a genus. This clarified IN 147’s structure as a Markush patent but did not resolve whether DAPA was disclosed, as the court focused on AstraZeneca’s admissions.
6. Ex parte Markush, 1925 CD 126 (Com.Pat. 1924): Implicitly referenced through Harnisch, this US decision established the legitimacy of Markush claims, allowing broad genus claims in chemistry. It provided historical context for IN 147’s claim structure, supporting its legal permissibility under Indian law (Section 10(5)).
7. FMC Corporation v. Best Crop Science LLP, CS(COMM) No.69/2021 and CS(COMM) No.661/2019 (Delhi High Court, July 7, 2021): Mentioned by AstraZeneca post-hearing to bolster their interim relief claim. The court distinguished it, as it involved a single patent, unlike the dual-patent claim involving a Markush structure in the present case.

Detailed Reasoning and Analysis of Judge

The Division Bench delivered a meticulous judgment, with the Markush patent issue at its core. The court framed the central question as whether DAPA, covered by IN 147’s Markush claim, was disclosed therein, impacting IN 625’s validity and AstraZeneca’s interim relief claim.

The court questioned AstraZeneca’s assertion of infringement for both IN 147 and IN 625, noting that claiming infringement of IN 147 implied DAPA’s disclosure therein, as infringement requires the infringing act to fall within the patent’s scope (Section 48). If DAPA was not disclosed in IN 147, no infringement could occur, undermining AstraZeneca’s dual-patent claim. The court emphasized that the Patents Act, 1970, limits a single invention to one patent with a 20-year term (Sections 2(j), 2(ja), 2(l), 3, 48). The identical field of invention descriptions in IN 147 and IN 625 suggested no technical advancement or economic significance in IN 625, raising doubts about its novelty and inventive step.

Regarding the Markush structure, the court acknowledged IN 147’s broad claim, covering millions of compounds but exemplifying only 80, none explicitly naming DAPA. Citing In Re: Harnisch, the court recognized Markush claims as a legitimate way to claim a genus under Section 10(5), allowing a group of inventions linked by a single inventive concept. However, AstraZeneca’s pleadings admitted DAPA’s coverage in IN 147, and their US actions—agreeing to align the US patent equivalent to IN 625’s term with IN 147’s and claiming infringement of IN 147’s equivalent—reinforced this admission. The court held that claiming infringement of IN 147’s Markush claim meant DAPA was disclosed therein, as coverage and disclosure are intertwined in infringement actions, aligning with Novartis’s broader interpretation but applying it factually to AstraZeneca’s admissions.

On obviousness, the court considered the defendants’ argument that IN 147’s example 12, disclosing a methoxy-substituted compound, was closeK close to DAPA’s ethoxy-substituted structure. The court found that a skilled person could substitute methoxy with ethoxy, both being lower alkyls, suggesting DAPA’s obviousness (F. Hoffman-La Roche). This rendered IN 625 vulnerable, as the Markush structure’s breadth did not negate the suggestive nature of its prior art.

The court also found AstraZeneca’s non-compliance with Section 8(2) of the Patents Act—failing to disclose USPTO objections and their response admitting DAPA’s disclosure in IN 147’s equivalent—further weakened IN 625’s validity. This non-disclosure was significant, as it could have influenced the Indian Patent Office’s assessment.

For interim relief, the court applied the triadic test: prima facie case, balance of convenience, and irreparable loss. AstraZeneca failed to establish a prima facie case due to IN 625’s vulnerability and their admissions regarding IN 147’s Markush claim. The balance of convenience favored the defendants, whose generics were 250–350% cheaper, serving public interest during the COVID-19 pandemic. The court noted that AstraZeneca could be compensated monetarily if they succeeded at trial, whereas injuncting the defendants would harm their market and public access to affordable drugs.

The court dismissed AstraZeneca’s arguments about IN 625’s long-standing validity (18 years) and global grants, as the Patents Act allows challenges at any stage (Section 13(4)). The differing reasoning in the two impugned orders did not warrant relief, as both denied injunctions without perversity (Wander Ltd.).

Final Decision

The High Court of Delhi dismissed all nine appeals, upholding the lower courts’ orders denying interim injunctions. The court imposed costs of Rs.5,00,000 on AstraZeneca for each suit, payable to the defendants, reflecting the appeals’ lack of merit and the judicial resources wasted by AstraZeneca’s parallel litigation strategy.

Law Settled in This Case

This case clarified several aspects of Indian patent law, particularly regarding Markush patents:

1. Single Invention, Single Patent: A single invention like DAPA cannot be protected by multiple patents with successive terms, as this violates the 20-year patent term limit (Sections 2(j), 48).
2. Markush Claims and Disclosure: Claiming infringement of a Markush patent implies disclosure of the invention therein, impacting subsequent species patents’ validity. Markush claims must fully disclose the claimed invention to support infringement actions (Sections 10, 25).
3. Inventive Step in Species Patents: Species patents following a Markush patent must demonstrate a distinct inventive step, such as technical advancement or economic significance, to avoid invalidation for obviousness or prior claiming (Section 2(ja)).
4. Section 8 Compliance: Non-disclosure of foreign patent examination details, especially objections, can render a patent vulnerable, even at the interim stage (Section 8(2)).
5. Interim Injunctions: A credible challenge to patent validity, combined with public interest factors like drug affordability, can preclude interim relief, with monetary compensation sufficing if the patentee prevails at trial.

Case Title: AstraZeneca AB & Anr. Vs. Intas Pharmaceuticals Limited

Date of Order: July 20, 2021

Case No.: FAO(OS)(COMM) 139/2020

Name of Court: High Court of Delhi 

Name of Hon'ble Judges: Justice Rajiv Sahai Endlaw and Justice Amit Bansal

Disclaimer: The information shared here is intended to serve the public interest by offering insights and perspectives. However, readers are advised to exercise their own discretion when interpreting and applying this information. The content herein is subjective and may contain errors in perception, interpretation, and presentation.

Written By: Advocate Ajay Amitabh Suman, IP Adjutor [Patent and Trademark Attorney], High Court of Delhi