Spotlight Back on Process Patents

In India, most people are conditioned to think that process patents went out of the window when India changed its 1970 Patent Act to introduce product patents, to make India’s patent regime compatible with the World Trade Organization’s Trade Related Intellectual Property Rights regime. That is wrong. Since 2005, India has had both product patents and process patents, subject to tough conditions meant to disallow extension of the life of a patent by minor alterations of the product or process.

Recently, Britain’s medical regulator, Medicines and Healthcare products Regulatory Agency substituted approving a particular drug with approving a method for making drugs that could be used for treating a range of related genetic diseases, each drug having to be tweaked to the specialised requirement of individual patients. On January 13, a girl suffering from an ultra-rare genetic disorder, affecting one in 50,000, received a version of a type of drug known as an anti-sense oligonucleotide, or ASO, reports The Economist. Nine other patients are slated to receive variants of the ASO, without these having been individually tested and approved by the regulator. What the regulator has approved is the protocol for producing the drug, measuring the effects of its passage through the body, and the narrow set of life-threatening genetic diseases, which could have variants depending on the constitution of the different individuals in whom these manifest, for which the ASO can be used as treatment.

These drugs bind with strands of RNA, distorting the message and protein coding instructions the RNA carries. This is expected to stop the treated girl’s cells producing faulty proteins responsible for her degenerative condition that could progress to fatal levels. This drug can be customised to treat different genetic conditions by altering the sequence of nucleotides, without altering their overall chemical formula. An ASO typically has 15-25 nucleotides.

In the normal course, each drug has to undergo clinical trials with a minimum number of patients and preponderance of evidence of safety and efficacy. The rarity of rare diseases makes this difficult, at the outset. When it comes to personalisation of a molecule to address the specific genetic fault in a particular patient, which might not be the same for another patient with very similar symptoms suffering from the same disease, standard clinical trials —controlled, randomized — become prohibitively expensive and time-consuming.

Once the safety and efficacy of a particular molecule is established, its further modifications by rearranging nucleotides, MHRA has determined, can be deemed to be safe and efficacious for treating a class of similar genetic disorders, each arrangement of nucleotides being adapted to the requirement of particular patients, without calling for approval and certification of particular nucleotide arrangements.

Each ASO then becomes a platform molecule, approved not for a particular condition but for any of a range of conditions. The approval process shifts from that of a product to that of a process of developing the molecule within a master protocol.

Indian drug companies spend more on research and development than other companies in India. But that is not saying much. The biggest Indian companies spend next to nothing on R&D. Two-thirds of R&D spending in India is done by the public sector. With all that, the combined R&D expenditure by India as a nation, at 0.65% of GDP, is smaller, in absolute terms, than the outlay by Amazon on R&D. Indian companies are not geared for foraying into genetic medicines.

Is the Indian law and regulatory apparatus ready for the shifting landscape in drug discovery and approval? That seems doubtful as well.

Section 3 of India’s patent law lays down what is not an invention and thus is not eligible for a patent. 3(d) reads as follows: 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.

When the nucleotides of a particular ASO are rearranged, it is chemically the same product. It does not enhance the known efficacy, rather it has a different efficacy, albeit slightly different in a person genetically slightly different. It does not result in a new product or employ a new reactant.

An ASO might receive a patent, but neither its different versions with rearranged nucleotides to be used to treat different individuals, permitted by its regulatory acceptance as a platform molecule nor the process of creating this diverse effects receive patent protection. Both the language of the law and how judges interpret the language need clarification, to make Indian patent law ready for personalised gene therapies.