Array BioPharma Sought Patent for Encorafenib-Based Dual and Triple Cancer-Drug Combinations; Delhi High Court Remands Application for Fresh Decision
Facts
Array BioPharma Inc. filed an appeal under Section 117A of the Patents Act, 1970 against an order dated 30 June 2023 passed by the Deputy Controller of Patents and Designs under Section 15 of the Act. The order refused Indian Patent Application No. 450/DELNP/2015, titled “Pharmaceutical Combination Comprising a B-Raf Inhibitor, an EGFR Inhibitor and Optionally a PI3K Alpha Inhibitor.”
The application claimed priority from a United States application filed on 7 August 2012. A Patent Cooperation Treaty application followed on 5 August 2013 and was published as WO2014/025688 on 13 February 2014. The corresponding Indian application was filed on 19 January 2015 and published under Section 11A on 26 June 2015. A request for examination was filed on 1 August 2016.
The First Examination Report was issued on 24 August 2018, and the applicant responded on 6 February 2019. After several hearings and adjournments, substantive written submissions were placed before the Patent Office. Nevertheless, the Controller refused the application on the grounds of lack of inventive step under Section 2(1)(ja), non-patentability under Sections 3(d) and 3(i), and objections concerning clarity and sufficiency under Sections 10(4)(c) and 10(5).
Claim 1 covered a pharmaceutical combination containing:
- Encorafenib, identified as Compound A and functioning as a B-Raf inhibitor;
- Cetuximab or Erlotinib as an Epidermal Growth Factor Receptor inhibitor; and
- optionally, Compound B, a PI3K-alpha inhibitor.
The claim permitted simultaneous, separate or sequential administration of the components. The dual combination consisted of Encorafenib with Cetuximab or Erlotinib, while the optional triple combination added the PI3K-alpha inhibitor.
The complete specification included experimental and clinical data. The appellant relied particularly on data showing that the dual combination of Compound A and Cetuximab restricted tumour progression to 12%, compared with 95% for Compound A alone and 88% for Cetuximab alone. The triple combination reportedly produced a change of minus 2%, indicating tumour regression.
The Controller nevertheless concluded that the combination lacked an inventive step, amounted to a method of treatment prohibited by Section 3(i), attracted Section 3(d), and did not sufficiently define its technical contribution.
Issues
The principal issues before the Court were:
- Whether the claimed pharmaceutical combination involved an inventive step under Section 2(1)(ja), particularly in light of prior-art documents D1 to D4.
- Whether the claimed combination was merely a method of treating human beings and therefore barred by Section 3(i).
- Whether Section 3(d), which restricts patentability of new forms or new uses of known substances without enhanced efficacy, was applicable to a combination of distinct active pharmaceutical agents.
- Whether the complete specification and claims satisfied the requirements of clarity, support and disclosure under Sections 10(4)(c) and 10(5).
- Whether the Controller had adequately considered the clinical data, the differences between the claimed compounds and the compounds disclosed in the cited prior art, and the alleged synergistic effect.
Appellant’s Arguments
The appellant argued that Claim 1 was expressly framed as a pharmaceutical product claim, not a process or method of treatment. The words “for simultaneous, separate or sequential administration” merely described how the components of the claimed combination could be used. They did not prescribe a therapeutic protocol, treatment sequence or physician-controlled process.
It was submitted that the claimed invention lay in the specific selection and combination of two or three active agents having different mechanisms of action. The dual combination consisted of Encorafenib with Cetuximab or Erlotinib, while the triple combination additionally contained a PI3K-alpha inhibitor.
The appellant relied on the experimental data in the complete specification to establish technical advancement and synergy. According to the appellant, the dual combination reduced tumour progression to 12%, while the triple combination achieved tumour regression of minus 2%. These results were said to be substantially superior to the results produced by the individual compounds or other two-drug combinations.
On Section 3(i), the appellant contended that the Controller had improperly fragmented the claim and treated references to treatment, dosing and administration as though they defined the invention. The claims, specification and disclosures had to be read as a unified whole. Clinical studies and dosing schedules were included to prove utility and workability, not to convert the product claim into a treatment method.
The appellant relied on Nestlé SA v. Controller of Patents and Designs and Medilabo RFP Ink Inc. v. Controller of Patents to argue that use of expressions such as “for treatment” does not by itself make a composition claim non-patentable under Section 3(i).
Regarding Section 3(d), the appellant submitted that the provision did not apply because the invention was not a new form, derivative, salt, ester, polymorph, metabolite or isomer of a known substance. It was a combination of distinct active pharmaceutical agents having separate chemical identities and mechanisms of action.
Reliance was placed on Ajantha Pharma Ltd. v. Allergan Inc., where the Intellectual Property Appellate Board had held that two independent active substances could not be treated as derivatives of each other merely because they were combined. The appellant alternatively argued that even if Section 3(d) applied, enhanced therapeutic efficacy was demonstrated by the clinical data.
On inventive step, the appellant argued that the Controller had neither identified the closest prior art nor properly formulated the technical problem solved by the invention. None of the cited documents disclosed the precise claimed dual or triple combination.
D1 disclosed Encorafenib but did not disclose its claimed combination with an EGFR inhibitor or the specified PI3K-alpha inhibitor. D2 concerned identifying tumours that may not respond to B-Raf inhibition and did not disclose Encorafenib as part of the claimed combination. D3 used different B-Raf and PI3K compounds, while D4 dealt with a PI3K inhibitor and addressed a different technical problem.
The appellant maintained that a person skilled in the art would have had neither motivation nor a reasonable expectation of success in selecting the exact claimed compounds from the broader classes disclosed in the prior art.
Respondent’s Arguments
The respondent defended the refusal and argued that the claimed invention was, in substance, a treatment regimen rather than a pharmaceutical product. The phrase “for simultaneous, separate or sequential administration” described how the medicines were to be administered to a patient and therefore formed part of a therapeutic protocol.
The respondent referred to the clinical-trial details in the specification, including oral capsules, tablets, intravenous infusions, frequency of administration and dosage schedules. These details, according to the respondent, demonstrated that the alleged invention lay in administering already known drugs to a patient rather than creating a new physical product.
It was argued that Encorafenib, Cetuximab, Erlotinib and the PI3K inhibitor were individually known and independently available. The applicant had not invented a new drug or formulation but merely proposed administering known compounds together.
On inventive step, the respondent submitted that D1, D2 and D4 could be combined by a person skilled in the art. D1 disclosed Encorafenib for B-Raf-mutant cancers. D2 disclosed combining B-Raf inhibitors with EGFR inhibitors, including Erlotinib and Cetuximab. D4 was said to disclose a relevant B-Raf and PI3K combination and to refer to EGFR inhibitors.
The respondent argued that the prior art supplied both motivation to combine and a reasonable expectation of success. Therefore, the claimed synergy was neither surprising nor unexpected.
The respondent further characterised the application as an attempt at evergreening and relied on Novartis AG v. Union of India. It also invoked public interest, arguing that granting a monopoly over a combination of independently available cancer medicines could adversely affect patient access.
Analysis of the Law
The Court first examined the precise compounds disclosed in D1 to D4 rather than accepting a broad class-based comparison.
D1 disclosed Encorafenib and contemplated pharmaceutical combinations, including combinations with several categories of therapeutic agents. However, while it referred generally to PI3K inhibitors, it did not disclose the specific PI3K-alpha inhibitor claimed in the application. Its disclosed combinations did not establish the exact claimed dual or triple combination.
D2 disclosed administration of an EGFR-signalling inhibitor together with a B-Raf inhibitor and specifically named Erlotinib and Cetuximab. However, it did not disclose Encorafenib. The B-Raf inhibitor used in its experiments was chemically different from the claimed Compound A.
D3 disclosed a B-Raf and PI3K combination, but the relevant compounds were not Encorafenib, Cetuximab, Erlotinib or the claimed PI3K-alpha inhibitor. The Court noted that the Controller had relied on experimental data involving materially different compounds.
The Court held that the Controller failed to explain which precise portions of D1, D2 and D4 would teach a person skilled in the art to select and combine the exact compounds claimed. It was not enough to identify broad classes of inhibitors and then reconstruct the invention by combining isolated disclosures. The objection based on lack of inventive step was therefore supported by inadequate reasoning.
On Section 3(i), the Court held that the claim had to be classified according to what it actually claimed. The phrase “for simultaneous, separate or sequential administration” functionally described the pharmaceutical combination. It did not impose a particular treatment protocol, dosing schedule, physician intervention or series of treatment steps.
The presence of dosage schedules and treatment examples in the specification did not alter the legal nature of the claim. Working examples demonstrate feasibility and practical implementation; they do not define the scope of protection. Since Claim 1 was framed as a product combination rather than a process, protocol or treatment regimen, the Controller’s reasoning under Section 3(i) was misplaced.
The Controller’s objections under Sections 10(4)(c) and 10(5) were also found to be unreasoned. The order merely stated that the claims lacked clarity and failed to disclose a significant technological contribution, without explaining the alleged defect. Since the Court had already found the Controller’s assessment of technical advancement inadequate, this objection also required fresh consideration.
The Court did not itself direct grant of the patent. Instead, it required the Controller to reconsider all objections afresh on the merits.
Precedent Analysis
Bayer Pharma Aktiengesellschaft v. Controller of Patents and Designs
The Delhi High Court had held that working examples demonstrate whether an invention is feasible and workable but do not define the boundaries of a patent. Patent scope is principally determined from the claims, interpreted in light of the description.
The Court applied this principle to reject the Controller’s reliance on dosing and treatment examples as proof that Array BioPharma’s claim was a method of treatment. The clinical examples supported workability; they did not convert a product combination into a process claim.
Societe des Produits Nestlé SA v. Controller of Patents and Designs
This decision recognised that a composition or product claim does not become a method-of-treatment claim merely because it refers to treatment or therapeutic use. The substance and framing of the claim must be examined.
The Court relied on this reasoning to hold that the expressions concerning administration were functional descriptions of the combination and not therapeutic method steps.
Ajantha Pharma Ltd. v. Allergan Inc.
The Intellectual Property Appellate Board held that the “combination” referred to in the Explanation to Section 3(d) does not necessarily encompass every combination of two independently active drugs. Two distinct active substances are not derivatives of one another merely because they are administered together.
The appellant relied on this authority to contend that its combination of separate active pharmaceutical agents fell outside Section 3(d). The Delhi High Court ultimately remanded the objections for fresh consideration rather than finally granting the patent on this basis.
Topotarget UK Ltd. v. Controller General of Patents and Designs
The Calcutta High Court considered disclosure requirements in pharmaceutical-combination patents and indicated that Section 10(4) does not require a separate working example for every conceivable embodiment falling within a claim.
The appellant relied on this case to support the sufficiency of its specification and to challenge the Controller’s simultaneous findings of insufficient disclosure and lack of inventive step.
Novartis AG v. Union of India
The respondent invoked Novartis to argue against evergreening and in favour of strict scrutiny of pharmaceutical patents under Section 3(d). The Court did not treat the judgment as automatically barring the present claim because the application concerned a specific combination of independent active agents, and the Controller’s analysis still had to address the exact statutory and scientific issues.
Zydus Lifesciences Ltd. v. E.R. Squibb & Sons LLC
The respondent relied on this decision to emphasise public interest and access to life-saving medicines. However, the Court did not accept public interest as a substitute for a proper statutory patentability analysis. The application had to be decided by applying the requirements of the Patents Act to the claims and prior art.
Court’s Reasoning
The Court found that the Controller’s inventive-step analysis suffered from a basic scientific and legal deficiency: it treated compounds belonging to broad therapeutic classes as though they were interchangeable with the specific compounds claimed.
Although the prior art disclosed B-Raf, EGFR and PI3K inhibition in different contexts, the Controller did not adequately demonstrate how those disclosures led to the exact combination of Encorafenib, Cetuximab or Erlotinib and the claimed PI3K-alpha inhibitor.
The experimental results in D2 and D3 involved compounds different from those claimed by Array BioPharma. The Controller nevertheless used those results to reject the appellant’s assertion of enhanced efficacy without properly accounting for the chemical differences.
The assertion that D1, D2 and D4 collectively taught the claimed combination was also unsupported by a step-by-step explanation identifying the relevant disclosures, motivation to combine them and reasonable expectation of success.
On Section 3(i), the Court distinguished between a claim directed to a pharmaceutical combination and a claim directed to the act of treating a patient. Claim 1 did not prescribe a process, protocol, dosing schedule or treatment regimen. It claimed a defined combination capable of being administered in different ways.
The Controller’s reliance on working examples was therefore legally incorrect. Treatment schedules in the examples showed that the invention could be implemented; they did not redefine the claim as a therapeutic process.
Finally, the objection concerning lack of clarity was stated in conclusory terms and did not explain why the claims failed to comply with Sections 10(4)(c) and 10(5). A reasoned reassessment was therefore necessary.
Conclusion
The Delhi High Court did not itself grant the patent. It remanded Patent Application No. 450/DELNP/2015 to the Controller for de novo reconsideration of the objections.
The Controller was directed to:
- provide Array BioPharma an opportunity of hearing;
- reconsider the application independently on its merits;
- decide the matter without being influenced by the Court’s observations as final findings on patentability; and
- dispose of the application within six months from receipt of the judgment.
The appeal was accordingly disposed of.
Case Details
Case: Array BioPharma Inc. v. Deputy Controller of Patents and Designs
Court: High Court of Delhi at New Delhi
Case Number: C.A.(COMM.IPD-PAT) 37/2023
Judge: Justice Tushar Rao Gedela
Judgment Reserved On: 18 May 2026
Judgment Delivered On: 23 July 2026
Patent Application: 450/DELNP/2015
Impugned Order: 30 June 2023
Relevant Provisions: Sections 2(1)(ja), 3(d), 3(i), 10(4)(c), 10(5), 15 and 117A of the Patents Act, 1970
Result: Patent application remanded to the Controller for de novo reconsideration and decision within six months after giving the appellant an opportunity of hearing.
