Pharmaceutical combination claims often require careful examination as they may involve known active ingredients. However, the claimed invention may be in the specific combination, its therapeutic effect or the manner in which the components work together. In such cases, objections under Sections 3(d) and 3(i) of the Patents Act, 1970 must be applied with precision. The distinction between the two provisions becomes important where the claim is directed to a pharmaceutical combination rather than a treatment process, protocol or dosing schedule.
The rejection of Array BioPharma Inc.’s patent application came under the scanner of the Delhi High Court in Array Biopharma Inc vs Deputy Controller of Patents and Designs [C.A.(COMM.IPD-PAT) 37/2023]. The patent application related to a pharmaceutical combination used for the treatment of proliferative diseases, including colorectal cancer. The respondent Controller had refused the application on the grounds of lack of inventive step under Section 2(1)(ja) and non-patentability under Sections 3(d) and 3(i).
The Court found merit in the appellant’s contention that Section 3(d) had not been properly applied, as the Controller had failed to identify the “known compound” of which the claimed invention was allegedly a derivative. The Court also relied on Topotarget UK Limited vs Controller General of Patents and Designs, Mumbai & Ors. [IPDPTA/50/2023], wherein the Calcutta High Court had held that a combination of two separate active drugs cannot be treated as derivatives of each other and would therefore fall outside the scope of Section 3(d).
The Court further found merit in the appellant’s contention that Section 3(i) was not applicable. It held that Claim 1 of the subject application was not framed as a process, protocol, dosing schedule or treatment regimen. Instead, claim 1 was directed to a pharmaceutical combination. Since Section 3(i) bars processes for treatment and not products or pharmaceutical combinations, the Court found that the reasoning for applying Section 3(i) was misplaced.
Factual Matrix
A patent application titled “Pharmaceutical Combination Comprising A B-Raf Inhibitor, An EGFR Inhibitor and Optionally a PI3K Alpha Inhibitor” was filed by Array BioPharma Inc. The claimed pharmaceutical combination is used to treat proliferative diseases, including colorectal cancer. The respondent Controller refused the application on the grounds of lack of inventive step under Section 2(1)(ja) and non-patentability under Sections 3(d) and 3(i) of the Patents Act, 1970. The applicant preferred an appeal against this refusal.
Appellant’s Case
On Section 3(d)
The appellant asserted that the given data clearly indicated the surprising and unexpected properties of the claimed invention using two or three specific drugs, in comparison to Compound A alone, Compound B alone, EGFR inhibitor alone, Compound A+B, or Compound B+Cetuximab. The appellant relied on the ruling of the Calcutta High Court in Topotarget case, wherein the Court emphasised that under Section 3(d) of the Act, a combination of two separate active drugs cannot be treated as derivatives of each other and therefore falls outside the scope of Section 3(d). The appellant contended that Section 3(d) is not attracted to a combination of independent active pharmaceutical agents.
On Section 3(i)
The appellant contended that the claimed invention is a combination product and not a method of treatment so as to fall under the exception stipulated under Section 3(i) of the Act. The appellant asserted that Claim 1 of the subject application provides a functional descriptor of the claimed pharmaceutical combination as a product and not as a method step. The appellant further contended that a combination of two or more actives is permitted and that the inventive concept or unexpected technical advantage is based on the final outcome and effect of the said combination. According to the appellant, the finding of the respondent that the claimed invention is a method of treatment of human beings and non-patentable under Section 3(i) was erroneous and unfounded.
On Inventive Step
The appellant inter alia submitted that each of the prior art documents D1 to D4 had been cited in counterpart patents granted in Australia, Canada, Europe and the United States.
Respondent Controller’s Response
The respondent contended that the claimed invention is a method of treatment, contrary to the submissions made by the appellant, and is therefore barred under Section 3(i) of the Act. The respondent asserted that Compound A is a known compound, Cetuximab is a known drug, Erlotinib is a known drug, and Compound B is a known compound, all of which are separately available. The respondent submitted that the appellant had not claimed any new physical product. Rather, what was claimed was the idea of giving these three known compounds or drugs to the same patient in sequence or simultaneously.
According to the respondent, this was a treatment process and therapy, and therefore the objection under Section 3(i) was not overcome. It was further submitted that if D1, D2/IPD2 and D4 are read together, a person skilled in the art working on B-Raf mutant colorectal cancer would have been motivated to use the triple combination of Compound A, EGFR inhibitor and Compound B. The respondent submitted that all individual elements were known, the combination was specifically taught, and the synergy was already demonstrated in the prior art for the same cancer in the same models.
Findings and Reasons of the Court
On Subject Invention
On perusal of the complete specification, the Court found that the present invention relates to a combination of a B-Raf kinase inhibitor and an epidermal growth factor receptor inhibitor, also known as EGFR, ErbB-1 or HER-1, and optionally, a phosphatidylinositol 3-kinase inhibitor, also known as PI3K. The combination is used for the treatment of proliferative diseases. The Court also noted that the specification refers to uses of such combination, pharmaceutical compositions of the combination of agents and methods of treating a subject suffering from a proliferative disease by administering a therapeutically effective amount of such combination.
On Cited Prior Art
The Court compared the claimed invention with the cited prior art and found that none of the cited prior art documents D1 to D4 specified the combination of Compound A, namely the B-Raf inhibitor Encorafenib, and Erlotinib/Cetuximab, namely the EGFR inhibitor. The Court also noted that the prior arts failed to disclose the combination of Compound A with Erlotinib or Cetuximab and, optionally, Compound B, namely the PI3K-α inhibitor Alpelisib.
On Section 3(d)
The Court found that, while invoking Section 3(d), the respondent Controller had failed to identify the “known compound” of which the claimed invention was allegedly a derivative. The Court held that the Controller had erroneously presumed the known compound from the compounds disclosed in the cited prior art, without specifying or identifying such compound in the impugned order.
On Section 3(i)
Analysing the respondent’s ground of refusal under Section 3(i), the Court held that Claim 1 was framed as a pharmaceutical combination and not as a treatment process, protocol or dosing schedule. The Court observed that the expression “for simultaneous, separate or sequential administration” was a functional descriptor of the claimed pharmaceutical combination and not a method step. Since Section 3(i) bars processes for treatment and not products or pharmaceutical combinations, the Court found that the reasoning for applying Section 3(i) to the subject application was misplaced.
The Delhi High Court accordingly set aside the refusal order and remanded the application to the respondent Controller for de novo reconsideration. The Court directed that the appellant be granted an opportunity of hearing and that the application be decided within 6 months from the date of receipt of the order.
Conclusion
This ruling clarifies that Section 3(i) does not apply merely because the claimed invention is for products or pharmaceutical combinations. Where the claim is directed to a product or pharmaceutical combination, and not to a treatment process, protocol, dosing schedule or regimen, the exclusion under Section 3(i) would not be attracted. The decision also reiterates that working examples or dosing details in the specification do not define the scope of the patent claim, and the claim must be interpreted on its own terms.
This ruling would encourage the patenting of pharmaceutical combinations involving multiple drugs, since Section 3(d) does not apply to pharmaceutical combinations. A combination of separate active drugs cannot be treated as derivatives of each other unless the Controller clearly identifies the known compound and explains how the claimed invention falls within the statutory exclusion.
Author: DPS Parmar