The Delhi High Court’s decision in Array BioPharma Inc. vs Deputy Controller of Patents and Designs [C.A.(COMM.IPD-PAT) 37/2023] is the first to acknowledge that a pharmaceutical combination claimed for simultaneous, separate, or sequential administration remains a product claim and is not excluded as a method of treatment under Section 3(i) of the Patents Act.

The appeal challenged the refusal of patent application number 450/DELNP/2015, entitled “Pharmaceutical Combination Comprising a B-Raf Inhibitor, an EGFR Inhibitor and Optionally a Pi3k Alpha Inhibitor”. The application claimed a pharmaceutical combination of two or three independent active pharmaceutical agents (APAs), namely a BRAF inhibitor, an EGFR inhibitor, and optionally a PI3K-α inhibitor, administered simultaneously, separately, or sequentially for treating proliferative diseases

Controller’s Findings

The Controller held that the claims were directed to a combination therapy rather than a pharmaceutical product, consequently falling within the exclusion under Section 3(i). According to the Controller, the expression “for simultaneous, separate or sequential administration” in claim 1, when read with the treatment schedule disclosed in the working examples, indicated that the inventive aspect lay in the therapeutic regimen rather than in a pharmaceutical product.

Further, the Controller held that the claimed invention lacked inventive step in view of the cited prior art documents (D1-D4), observing that all three individual compounds in claim 1 ((a) Compound A (encorafenib), a B-Raf Inhibitor, (b) Cetuximab/Erlotinib, a EGFR Inhibitor and (c) Compound B (PI3K-α Inhibitor)) were already known and that combining them would have been obvious to a person skilled in the art (PSITA).

The application was also refused under Section 3(d) on the ground that the claimed compounds were a derivative of the known compounds from D1-D4, relying on the same reasoning applied under the inventive step objection.

Appellant’s Contentions

On Section 3(i): The Appellant submitted that the Controller had fundamentally misconstrued the nature of the claims. The claims were directed to a pharmaceutical combination (a product claim), and not to any method of treatment. The expression “for simultaneous, separate or sequential administration” merely served as a functional descriptor indicating the possible modes in which the claimed combination could be administered. It was further contended that the use of expressions such as “treatment” or “administration” neither altered nor defined the inventive concept, which lay in the combination itself and the unexpected synergistic therapeutic effects and the resulting technical advantages.

On Section 3(d): The Appellant argued that Section 3(d) was inapplicable to the present invention since the claims concerned a combination of distinct and independent APAs, not to a new form, salt, ester, ether, polymorph, metabolite, isomer or any other derivative of a known substance. It was submitted that the expression “combination” in the Explanation to Section 3(d) refers strictly to a combination of derivatives enumerated therein, or a combination of one or more such derivatives with the known substance itself, not a multi-API combination.

On inventive step: The Appellant pointed out that the impugned order lacked cogent reasoning. Further, none of the cited prior art documents, individually or in combination, disclosed or suggested: (i) the specific B-Raf inhibitor Encorafenib (Compound A); (ii) the specific EGFR inhibitors Erlotinib or Cetuximab; (iii) the specific PI3K-α inhibitor Alpelisib (Compound B); or (iv) the claimed dual combination comprising Encorafenib with Erlotinib/Cetuximab or the claimed triple combination comprising all three agents. Furthermore, the applicant demonstrated technical advancement through improved, therapeutically relevant selectivity achieved by the specific combination.

Court’s Observations

Pharmaceutical Combination vs Method of Treatment

The central question before the Court was whether including the phrase “for simultaneous, separate or sequential administration” in the claim language converts an otherwise patentable product claim into a non-patentable method of treatment under Section 3(i).

Answering in the negative, the Court observed that this language merely operates as a functional descriptor defining different ways in which the constituent active ingredients forming part of the combination may be administered. It does not add method steps into a product claim.

The Court further clarified that references to dosage schedules or administration regimens in the working examples explain the practical implementation of the invention, they do not define or restrict the scope of the claims.

Inventive Step

The Court found that the Controller’s conclusion on inventive step was unsupported by a reasoned analysis. While the Controller identified individual elements across disparate prior art references, they failed to establish how a PSITA would be motivated to select and combine these specific compounds with a reasonable expectation of success.

On examining each of the cited prior art documents, the Court noted that none of them, either individually or collectively, disclosed or suggested the claimed pharmaceutical combinations.

With respect to technical advancement, the Court observed that the Controller had rejected the appellant’s clinical data by relying upon efficacy data disclosed in D2 and D3, ignoring the fact that those disclosures involved different BRAF and PI3K inhibitors. Since the prior art relied upon different compounds from those claimed in the subject application, the Controller ought to have to explain how the comparative data could negate the technical advancement of the claimed combinations.

Section 3(d)

The Court observed that the impugned order failed to identify the known compound from which the claimed combination was allegedly derived.

Referring to the Calcutta High Court’s decision in Topotarget UK Limited vs Controller, the Court reiterated that Section 3(d) applies to new forms or derivatives of a known substance and that a combination of two separate active drugs cannot be treated as derivatives of each other and therefore fall outside the scope of Section 3(d).

The Court further observed that the Controller had relied upon the reasoning recorded under the objection of lack of inventive step to reject the data on efficacy. However, even while dealing with inventive step, the Controller had neither identified the alleged known compound nor established that the cited prior art disclosed the claimed combinations. Therefore, the same was held to be unsustainable.

Decision

In view of the above findings, the Court set aside the impugned order and remanded the matter for de novo reconsideration of the objections raised.

Key Takeaways

• A pharmaceutical combination claim does not become a method of treatment merely because it is claimed for simultaneous, separate or sequential administration. Such language merely serves as a functional descriptor of the claimed product, rather than a method step.
• The nature and scope of an invention must be determined from the claims and not from the working examples in the specification. While working examples demonstrate the workability and practical implementation of an invention, they do not define or limit the scope of the claimed invention.
• The mere existence of individual components in the prior art is insufficient to deny inventive step.
• Section 3(d) cannot be invoked against pharmaceutical combination inventions involving known active pharmaceutical ingredients.
• For invoking Section 3(d), the Controller must identify the “known substance” and establish how the claimed invention constitutes a new form or derivative thereof. Failure to identify the known substance renders the objection unsustainable.