Patenting incremental innovations: Advantage India

After our success in business process outsourcing, it is time we proved our mettle in research process outsourcing, says Dr Viraj Suvarna

Necessity is the mother of innovation. And who knows this better than the Indian pharmaceutical companies, some of which are now multinational. Since the 1970s when process patents replaced product patents for pharmaceuticals, Indian companies have made hay while the sun shone. Reverse engineering is their forte and they used it to the hilt in getting new chemical entities (NCEs) to the Indian market within a few months of the multinational company (MNC) launching the product.

Speed to market is of essence and soon we had examples of the Indian company launching the product within days of the MNC launch. Now we even have examples of an Indian company launching the product before the MNC can do so. In the days to come this may become difficult since product patent has been introduced in our country from January 1, 2005. A larger number of the non-R&D based Indian companies are trying their best to seek loopholes within the law. It is their contention that India is in a perpetual health crisis and compulsory licensing is applicable for most conditions.

However, the government seems to be firmly resolved to introduce an effective product patent regime in the country, and adhere to commitments made when India became a signatory to the WTO pact. Against this backdrop it seems a little surprising that such a hue and cry is being made about whether product patents need to be granted for NCEs only or for products on which incremental innovation has been made over and above the NCE, or for both.

Given the strengths and competencies of Indian pharmaceutical companies, it seems that patenting incremental innovations would make the best sense. One only has to compare examples of their successes with incremental innovations to failures with NCEs. Examples of the latter include ragaglitazaar, balaglitazone, and the recent parvosin. Barring a few examples of drugs from CDRI, Lucknow which have not been commercial successes, one cannot recollect a single example of an Indian company being able to successfully discover and launch a new chemical entity. On the other hand, Indian pharmaceutical history is replete with examples of innovative improvements to existing science. Incremental innovations can result from many techniques, e.g., new drug delivery systems, new salts, enantiomers, isomorphs, etc.

Take the case of the alpha blocker, prazosin. Applying the GITS technology to prazosin has certainly improved its benefit to risk ratio and Indian companies are capable of formulating an indigenous osmotic pump controlled drug delivery system that, if found equivalent to the Alza patented GITS technology, can bring in considerable revenue as MNCs worldwide would then want to shift to the Indian new drug delivery system (NDDS).

While on this topic, Ranbaxy recently introduced an improvised delivery system which enabled ciprofloxacin to be given once daily instead of the usual twice daily. This was in-licensed by Bayer, the makers of ciprofloxacin. India has the distinction of coming out with the only parenteral and gel formulation of rofecoxib and intramuscular formulation of ciprofloxacin in the world.

While the world is debating on the need to combine an angiotensin converting enzyme inhibitor (ACEI) with an angiotensin receptor blocker (ARB) and is doing studies on the free dose combination, India has gone ahead and marketed the first ever fixed-dose combination of an ACEI, ramipril with an ARB, losartan. These may not seem such great advances over existing molecules but certainly provide a unique differentiating feature that can be the stepping stone for other quantum leaps.

Emcure Pharmaceuticals in collaboration with National Chiral Laboratory, Pune, marketed the s-isomer of amlodipine and have gone on to do the same with atenolol and combinations of the same with other drugs such as ACEI or atorvastatin. If they get a patent on these products they enjoy exclusivity and can even hope to export the same provided their data is found adequate by the regulators of those countries. Other examples of Indian innovation, not necessarily always patentable based on NINSU (N - Novelty, INS - Inventive Step, U - Utility or industrial applicability) criteria, are the stable technology for vitamin B12, homocysteine lowering vitamin combination, and the much talked about polypill which is expected to be developed in India this year.

It is a peculiar situation now that MNCs are interested in India as a market and most Indian companies are looking outward. In fact some Indian MNCs get more of their revenue from sales abroad than in India. If only NCEs get patent protection, then it will be increasingly difficult for Indian companies to compete because of their proven track record in the past. Also if one looks at the world scenario very few NCEs have really come to market.

The cost and uncertainty/risk of drug development is only escalating, the Tufts Study estimating that it would cost US $897 to bring a molecule to market. Lehmann Brothers has projected that this would increase to US $1.6 billion. Naturally companies are seeking to merge to create entry barriers and maximize product portfolios and pipelines. Indian companies have either acquired or are into arrangements with foreign companies which will also help them in case an MNC wishes to partner with them in marketing/local clinical development of product.

What could be the possible reason for Indian companies to shun from seeking patent protection for their efforts at incremental innovation? They have their eyes firmly set on the US and other major markets which afford greater revenue in terms of value than the poor purchasing power volume-driven Indian market. In those markets they know that their incremental innovations can get patent protection.

What would they gain from patenting the same in India? However, who stands to lose from this approach. The resident Indian scientists and entrepreneurs who have the capability to make those incremental innovations but don’t have the wherewithal to apply for patent protection abroad. If they do not get patent protection for their efforts they are less likely to be incentivised to do so, knowing fully well that their data will no longer be confidential and can be copied by all and sundry. This might sound the death knell for indigeniuses.

Indian MNCs are also wary of making incremental innovations patentable because they perceive that the big bad MNCs might use this route to extend their original patent. They are of the mistaken belief that the originator will make incremental innovations to NCE in a bid to extend patent protection or delay loss of exclusivity. Let’s take the example of omeprazole. When loss of exclusivity was on the horizon, Astra-Zeneca launched Nexium or esomeprazole and tried to convert existing prescribers of Prilosec (omeprazole, biggest selling product before Lipitor) to Nexium. Did it work? Not really.

What people don’t realise is that the patent for the original omeprazole does not get extended. All that the MNC gets is a fresh patent on esomeprazole while generics are free to copy omeprazole. Doctors are naturally wary to try our new drugs and would prefer to stick by the tried and tested drugs. While the innovation may seem incremental, the sales generated are as incremental as the difference between an omeprazole and an esomeprazole. The cost of promotional efforts to make customers perceive marginal differences between the two molecules may prove counter-productive.

As Indians we need to be more confident of our ability to innovate and our efforts deserve to be patented. If we don’t patent it, someone else will. We also need to think of the fact that in many research laboratories abroad Indian scientists hold very important positions. If they can do it there why not here? As Dr Enas Enas has rightly said, ‘‘If genes load the gun, environment pulls the trigger.’’ We need to create conditions that reverse the brain drain. If we could do it in information technology, why not in innovator technology?

We are stunning the world with our competence in business process outsourcing (BPO). Why not in RPO (research process outsourcing) or Big Pharma innovation? Let us also remember that R&D-based MNCs plough a significant part of their profits back into research and development and thus sustain themselves. By killing the golden goose we are only pulling our own noose. As for the ‘cost’ of medicines we need to know that there is a ‘price’ we have to bear if we do not ‘pay’ attention to health. Health is our greatest wealth, more valuable than the costliest medicine, and we realise that only when we lose it. The value that medicines bring may make them dear but that can also serve as an incentive for us to stay fit and not take our health for granted.

The writer is Medical Advisor, Pfizer Limited. E-mail: viraj.suvarna@pfizer.com