The Indian patent office strikes again – patent application refused as chemical variant of known compound is not considered an invention according to Section 3(d)

In a recent decision, the Indian Patent Office rejected a patent application from the Applicant Gilead referring to vaccines against Hepatitis C and methods of their manufacture (Appl. no. 6087/DELNP/2005). Despite the fact that the subject matter of the claims was found to be both novel and based on an inventive step, the application was rejected as the subject matter of the claims was not considered an invention based on the infamous Section 3(d) in the Indian Patents Act.

The decision raises several questions based on different objections referred to during the examination proceedings of this application. Certainly the most interesting objection is the objection based on Section 3(d) of the Indian patents act.

Background: Section 3(d)

Section 3 of the Indian Patents Act defines “What are not inventions”. According to subparagraph (d):

“the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use of a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant.

Explanation: For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy”

Section 3(d), which was introduced in the 2005 amendments of the Indian patents act, is intended to protect against patenting of trivial improvements of known molecules. It was put in place to avoid that patents directed to pharmaceutical compositions are filed again and again with slight modifications to provide a continuous patent protection beyond the 20 year term of the basic patent.

As highlighted in Section 3(d) above, to avoid undue patent protection, a new form of a known substance is only considered a patentable invention if it results in enhancement of the known efficacy of the substance.

In an earlier, memorable decision of the Indian High Court, namely Novartis A.G. vs. Union of India & Others, the Indian Supreme Court rejected the Novartis Gleevec/Glivec patent based on Section 3(d), claiming that the beta crystal form of imatinib mesylate would not show an enhanced efficacy as required by Section 3(d).

In the earlier decision of the Indian Supreme Court, Novartis argued that imatinib mesylate shows an increased efficacy as it had a 30% increased bioavailability compared to imatinib. Novartis also proved that imatinib mesylate has better physicochemical properties, such as better flow properties, better thermodynamic stability and lower hygroscopicity.

During these proceedings, the Court did not discuss what kind of data would suffice in establishing enhanced efficacy and relied on a medical dictionary definition to opine that ‘efficacy’ means ‘therapeutic efficacy’. Therefore, the Court rejected Novartis’ arguments as the improved properties of imatinib mesylate would not demonstrate better “therapeutic efficacy”.

Keeping this earlier decision of the Supreme Court in mind, the Deputy Controller of Patents argued in the present application from Gilead that because the Hepatitis C vaccine claimed in the present application is only a stereo-isomer of a known compound, it would have to show enhanced ‘therapeutic efficacy’. According to the Deputy Controller of Patents, Gilead failed to demonstrate that the claimed Hepatitis C vaccine showed such an enhanced ‘therapeutic efficacy’.

Gilead provided comparative data demonstrating that the Hepatitis C vaccine as claimed showed reduced cytotoxicity without compromising in its ability in treating Hepatitis C, when compared to other substances used for treating Hepatitis C. The question is whether this type of data is sufficient to show an enhanced ‘therapeutic efficacy’.

We remember that in the previous case of Novartis A.G. vs. Union of India & Others, the Indian Supreme Court rejected data showing an increased bioavailability of the claimed product, stating that no link could be established between increased bioavailability and an increase in ‘therapeutic efficacy’.

In light of these guidelines from the Supreme Court and the understanding of Gilead´s experimental data by the Deputy Controller of Patents, it therefore `appears´ only consistent with the earlier rulings that the Indian patent office reject Gilead´s patent application, arguing that the reduced cytotoxicity would be insufficient to prove significant increase in the therapeutic efficacy as there would be no link between the reduced cytotoxicity and enhanced therapeutic efficacy.

However, more often than not, the devil is in the details of the decision. Firstly, in earlier decisions of the Indian patent office it was decided that a reduced cytotoxicity is indeed a factor that needs to be considered in assessing enhancement of therapeutic efficacy (e.g. 106/DELNP/2008 and 413/MUM/2003). Secondly, in the decision to reject Gilead´s patent application, it is stated that “[t]herapeutic efficacy may be proved by showing clinical trials so as to prove significant difference in the properties with regard to efficacy … The data [provided by Gilead] does not show any clinical trials to prove the improvement in the therapeutic efficacy …”

Even though the decision to reject Gilead´s patent application is not very specific on which of the above points actually lead to the rejection of the application, Applicants of Indian patent applications can only hope that in future examination proceedings, the presentation of clinical data will not be made a requirement for showing increased therapeutic efficacy. After all, Section 3(d) does not define any specific type of information required to show enhanced therapeutic efficacy and even the Supreme Court stated in Novartis A.G. vs. Union of India & Others that results from animal studies could be suitable to show enhanced therapeutic efficacy.

It was also discussed in different forums, after issuance of the Gilead decision, whether the fact that the data Gilead provided, which did not show any comparison with the compound referred to in the closest prior art, was a reason for the rejection. Unfortunately, the decision does not provide a clear answer to this question. Like the question of the possible necessity of clinical data vs in vitro or non-human animal test data, it would seem less plausible if the question of enhanced therapeutic efficacy is necessarily connected to a compound cited in the prior art since there might be many ways to show enhanced therapeutic efficacy.

We can only hope that Gilead will file an appeal against this decision so that we may gain further insight as to why the present application was rejected and whether the rejection was justified.