Array Biopharma INC v. Deputy Controller of Patents and Designs: A case study

In a significant ruling on the patentability of pharmaceutical combination inventions, the Delhi High Court set aside an order from the Indian Patent Office refusing the grant of a patent for a triple-drug combination used in cancer treatment, under Indian Patent Application No. 450/DELNP/2015, titled "Pharmaceutical Combination Comprising a BRAF Inhibitor, an EGFR Inhibitor and Optionally a PI3K Alpha Inhibitor.

Aggrieved by the rejection from the Indian Patent Office, the Appellant approached the Delhi High Court by filing an appeal under Section 117A.    

The order deals with the standards for assessing inventive step in combination-drug applications, combinations not falling under the scope of Section 3(i) and the derivative-substance bar under Section 3(d) besides Sufficency of disclosure.

Combination claims do not  fall under the prohibitions of  Method of Treatment under Section  3(i):-

The Controller held that the claim fell under Section 3(i), which precludes from patentability any process for the medicinal, surgical, curative, prophylactic, diagnostic, therapeutic or other treatment of human beings. Besides referring to the dosing regimen disclosed in the specification, the Controller  based his reasoning  on the concluding phrase in claim 1 "for simultaneous, separate or sequential administration," to reach this conclusion.

Referring to the judgments in the cases of Nestle SA and Medilabo RFP Inc., the Appellant vehemently argued that the claim relates to a product per se and not a method of treatment. Applellant  also argued that mere disclosure of a functional descriptor on how a combination may be administered does not convert a product claim into a process claim.  

The Respondent countered by referring to the therapeutic protocol and dose-escalation clinical trial data disclosed in the specification and contended that the inventive contribution was a treatment regimen combining three independently known and commercially available drugs, amounting to impermissible "evergreening" besides falling the invention under the preclusion of Section 3(i).

The Court ruled in favour of the Appellant and held that claim 1 of the subject application is not framed as a process, a protocol, a dosing schedule, or a treatment regimen, thereby rejecting the objection under Section 3(i).Applicability of Section 3(d) on Combination Claims:

Section 3(d) precludes  from patentability a "mere discovery of a new form of a known substance " that does not enhance known efficacy, and its explanation extends this bar to "combinations of known substances" unless they differ significantly in properties with regard to efficacy.In a very curt observation, the Controller held that the claimed combination was "known from the prior art" and therefore fell under Section 3(d).

Without identifying which specific "known substance" the claimed combination was allegedly a derivative of, the Appellant, relying on the IPAB's decisions in Ajantha Pharma Ltd. and the Calcutta High Court's ruling in *Topotarget UK Ltd.  argued that a combination of two or three independent active pharmaceutical agents, cannot be treated as a "derivative" of the other and therefore falls outside Section 3(d).

Besides, without prejudice, referring to the clinical trial data and dosing schedules in the specification demonstrating the efficacy of the combination, the Appellant emphasized on the synergistic interaction of the specific compounds as a defined combination product  to argue that  the rejection under Section 3(d) lacked merit.

Agreeing with the Appellant, the Court held that the Controller had erroneously presumed the known compound from the compounds disclosed under the cited prior art, which was neither specified nor identified in the impugned order. The objection under Section 3(d) was accordingly rejected.

Lack of Inventive Step Under Section 2(1)(ja):

In rejecting the case on this ground, the Controller relied on four prior art documents (D1to D4) and contended that reading them together, a person skilled in the art (PSITA) would have been motivated, with a reasonable expectation of success, to arrive at the claimed combination. The documents cited were D1 (W02011025927),  D2 (WO2011025927)  D3 (WO2011046894) and D4 (WO2011029082).

Appellant presented a very detailed explanation of each cited document to conclude that none of cited documents , individually or in combination, disclosed or suggested  the specific  claimed combination of Encorafenib + Erlotinib/Cetuximab +  PI3K-a Inhibitor. 

The Court undertook a very detailed document-by-document comparison of all the cited documents and gave its findings. 

For D1, the Court held that it does not disclose the PI3K-a inhibitor specified in Claim 1 of the claimed invention. On D2, the Court held that the RAF inhibitor used in para 51 of D2 is different from the Encorafenib claimed in claim 1 of the impugned application. On D3, the Court held that it relates to a combination of B-Raf inhibitor dabrafenib and PI3K inhibitor; it does not  disclose encorafenib and the PI3K-a inhibitor, namely alpelisib, as claimed in the impugned application. On D4, the Court held that it did not specify the EGFR and PI3K-a inhibitor as claimed in the subject application. 

The Court concluded that none of the cited prior art D1 to D4 specify the combination of compound A (B-Raf Inhibitor), Encorafenib, and Erlotinib/Cetuximab (EGFR inhibitor). Further, the prior arts D1 to D4 also fail to disclose the combination of compound A (B-Raf Inhibitor), Encorafenib, and EGFR inhibitors Erlotinib or Cetuximab and optionally, Compound B, i.e. PI3K-a inhibitor (alpelisib).

Besides examining the cited documents in much detail, the Court also delved deeper into the aspect of technical advancement.

The Court  held that after analysing the data disclosed in the complete specification,   the Controller rejected the enhanced efficacy  provided under examples 2 and 3 of the specification  of subject application, in view of the data from D2 and D3,   however, teh Controller fatally, does not discuss that the compounds used are BRAF and PI3K-a inhibitors which are not the same as disclosed in prior arts D1 to D4.

After detailed analysis of the data disclosed in the specification and the prior art , Court rejected the objection of lack in inventive step and the reasoning given by the Controller. Consequently, the reasoning on lack of inventive step was found unsustainable.

Sufficiency of Disclosure (Sections 10(4) and 10(5):

The impugned order held that the claims are not clear and sufficiently definitive to the scope of the invention in the absence of mention of any significant technological contribution over the prior art cited documents.

The Appellant successfully challenged the Controller's cursory findings that the claims lacked clarity and sufficient definitiveness under Sections 10(4)(c) and 10(5),

The Court observed that in the absence of any reasoning provided by the Controller  this objection needed to be reconsidered afresh.

Besides the aforementioned grounds, the Appellant strongly  pointed to the grant of counterpart patents in major foreign jurisdictions citing that those patents were granted after considering the same citations, whereas the Respondent pleaded public interest.

However these  issues were not commented upon by the Court.  

The Delhi High Court set aside the impugned order in its entirety and remanded the application to the Controller for de novo consideration of all objections, to be decided within six months.

Conclusion: Combination not falling under Section 3(i)- Inspite of specification disclosing  dosing and administration regimen, a combination claim  will not automatically be rejected as a "method of treatment" under Section 3(i).

Identification of relevant Prior art for objection under Section 3(d) -  A bare assertion that a combination is "known from the prior art" is insufficient; the Controller must specifically identify the known substance of which the claimed subject matter is said to be a derivative, and combinations of independent, distinct active agents generally fall outside Section 3(d)'s Explanation.

Obviousness analysis demands an articulated motivation to combine-  unless the Controller explains why and how a PSITA would be motivated to combine those specific teachings with a reasonable expectation of success, cherry picking from  multiple prior art documents would not be considered sufficient to establish obviousness.

Working examples do not define the scope of invention- Referring to Bayer's case , Court observed that the working examples are essential for demonstrating the feasibility and workability of an invention but they do not define the patent's scope.

This order is significant from the perspective of combination inventions in India.

Ranjna Mehta-Dutt 

Partner | Attorney at Law | Patent Attorney

ranjnamehtadutt@iprattorneys.com