The real meaning of 'efficacy'

In 2005 India amended the Patents Act to introduce protection for product inventions, including patents for pharmaceuticals. Section 3(d) of the Patents Act was qualified with the phrase 'enhanced efficacy' for new forms of known substances as a test for being considered an invention. However, the absence of a definition for the term 'efficacy' raised many challenges. The exact meaning and elucidation of the phrase 'enhancement of known efficacy' was open to interpretation, and was eventually addressed by the Supreme Court.

What is efficacy?
The Supreme Court clarified that efficacy must be seen in the desired or intended use of the product of the invention, and that in the case of medicines, whose function is to cure disease, the test of efficacy can be only “therapeutic efficacy”. Although efficacy was introduced as a powerful testing tool for patentability to prevent evergreening, the definition has presented many challenges to applicants where therapeutic efficacy is expected for inventions or products unrelated to drugs.

Recently, the actual intent of the Supreme Court’s decision on the definition of 'efficacy' has become clear. When a product is not related to a drug, the Indian Patent Office (IPO) accepts the enhancement of efficacy in the intended or desired use of the invention. It is generally understood that an optimum value or certain numeric range for efficacy cannot be predicted for pharmaceutical products.

However, for pharmaceutical inventions, not all types of efficacy are considered to satisfy Section 3(d) or meet the therapeutic efficacy definition, such as:

• low toxicities of the claimed compounds;
• comparative kinase selectivity tests;
• physical parameters such as stability; and
• the formation of crystals.

In general, the IPO has not considered these features favourably. Following the Supreme Court’s 2013 decision in Novartis v Union of India, in which the court did not consider increased bioavailability to be an enhancement in therapeutic efficacy, applicants and examiners have yet to decide what constitutes therapeutic efficacy.

Acceptable data
While reviewing the type of information or data that can be accepted in cases where inventions have been objected to under Section 3(d), the IPO has considered:

• the IC₅₀ (provided by the applicant in comparison to the IC₅₀ of the prior art compounds);
• improved therapeutic efficacy over the product of the cited art, which in turn has a low thixotropic index (relating to viscosity);
• improved ability to flow;
• formation of crystalline solvent-free salts which are more stable in a solid state than the prior art compound and have a higher melting point;
• the potency being at least 10 times more than that of the prior art compound;
• improved 5-HT4 receptor agonistic activity (relating to serotonin receptors); and
• unexpected high activity against a hepatitis virus.

General practice
The IPO has also considered inventive step, and Section 3(d) together with the lack of inventive step, as being due consideration in rejecting a case under Section 3(d).

Next steps
Thus, on a case-by-case basis, the onus is on the applicant to link the properties related to the efficacy of a new form with enhanced therapeutic efficacy. Characteristics such as lower toxicity, higher potency and a comparison of clinical studies of healthy and sick patients showing a significant improvement in their conditions can be interpreted as enhancement in therapeutic efficacy. The evaluation as to whether a metamorphosis in properties is inter-related to efficacy is significant and should be considered with reference to assessment by a person skilled in the relevant art.

One of the key factors could be identification of the change in a drug’s pharmacological effect due to the new form compared to the known form, and linking it to therapeutic efficacy. While not all properties may affect the pharmacology, identifying the specific properties which have an effect is important.

Comment
There may still be grey areas surrounding what suffices as enhanced therapeutic efficacy. The IPO appears to accept clinical trial data to overcome Section 3(d). However, if such clinical trial data is not available at the time of filing the patent application, external evidence is acceptable, as seen in Novartis v Union of India.

As decisions from the IPO, the Intellectual Property Appellate Board and the courts continue to define the meaning of 'efficacy' and how it can be interpreted to protect genuine inventions, the scope and limitations of Section 3(d) should become clearer in the near future. While lack of awareness is a major reason for difficulty in interpreting Section 3(d), it should not be misinterpreted as prohibiting efforts of researchers. As the IPO also tries to clarify various procedures to expedite prosecution, this is an exciting time of continuous and progressive development for applicants and legal practitioners.