Novartis’ Cancer Drug (Gleevec) vs. the Supreme Court of India: a Classic Catch-22?

Indian Supreme CourtThe ruling the other day by the Indian Supreme Court to deny Swiss global pharmaceutical company Novartis AG’s patent appeal for its cancer drug Gleevec (Imatinib) has been called landmark for many reasons. In fact, there have been dozens, if not hundreds of articles in newspapers, journals, blogs and much coverage in all media. Here are but a few examples that are not intended by any means to be exhaustive but merely illustrative of the issues being brought forward.

Novartis denied cancer drug patent in landmark Indian case (Globe and Mail)

Novartis Cancer-Drug Patent Denied by India Supreme Court (Bloomberg News)

Low-Cost Drugs in Poor Nations Get a Lift in Indian Court (New York Times)

The Novartis Decision: Is the Big Win for Indian Pharma Bad News for Investment? (Time World)

Supreme Court’s Glivec ruling will ruin innovation, says Ranjit Shahani, Novartis India MD (The Economic Times)

Indian Supreme Court Decision on Novartis Case a Victory for Access to Medicines in Developing Countries (Doctors Without Borders/Médecins Sans Frontières)

India’s generics drug ruling will help, not hinder, innovation (Globe and Mail)

As can be seen, there are many who feel adamantly that this is a huge blow to the protection of Intellectual Property (IP) and that it will create an atmosphere where companies, not just pharma companies, will refuse to do R&D in India if their IP is treated so cavalierly. On the other side of that argument are heath advocates who insist that this ruling has been a huge win for all those in developing countries who cannot afford expensive drugs and who rely on much cheaper generic versions for their health and well-being. Like all complicated issues, I suspect the truth indeed lies somewhere in between.

Given the HUGE volumes that have already been written, at first I thought it was folly to even think about jumping into the fray.

I am still reticent, on the fear that there is little hope of me adding anything salient or constructive to a story that has already been intensively covered, and by experts far better versed in the issues than I will ever be. What could I add that legal experts, business journalists, pharma experts, heath care advocates and activists etc.  have not already said? Possibly nothing, but as I read so many of the accounts I just felt that there was still something missing, something that bothered me about the whole thing.

Part of it is that I have a very “soft spot” for Gleevec. Indeed I have written about Gleevec in these very pages (see my blog post on rational drug design and Gleevec), but see also my mentions of Gleevec in at least 3 other posts (here; here; and here). Why is Gleevec so important? As I outlined in the first linked article, Gleevec was the proof of principle, the poster child, if you will, of rational drug design. The idea that if you know what the underlying mutation was that was causing the cancer in question, in this case Chronic Myelogenous Leukemia (CML), then you may be able to effectively DESIGN a drug to treat it. The whole era of genomics and personalized medicine that I have also written extensively about follows on from this concept. Gleevec represented a true sea-change in cancer treatment and its importance should not be easily dismissed or understated.

And this was the first thing that really nagged at me: if Gleevec was not a breakthrough in the way we think about cancer treatments, then I don’t know what is! And yet here was the Supreme Court of India saying that the patent application/appeal was being denied because the molecule in question was not innovative enough! Not innovative? Are you kidding me?

How could a drug that has been patented in the USA and perhaps a few dozen other countries be innovative enough for IP protection around the world yet not in India?

That’s when I learned that maybe the drug under appeal was NOT the same as the original Gleevec… So, was this Gleevec or was this some derivative of Gleevec that was the subject of the appeal/application? I went back and searched some more to try and solve this riddle.

And that’s when I learned about the term “evergreening”. Simply put, evergreening is the process whereby a patent holder (like Novartis) creates second or third generation compounds related to the original but which are different enough that they can claim new patent protection for the “new” drug.

On the surface, this seems inherently OK to me – the whole process of drug development is to refine, refine, refine. Get rid of side effects, increase efficacy, make it better. If you can do that, and the next  generation compound is very different from its ancestors, why can this not be protected as well?

The tricky part, of course, is that the improvements have to be genuine and demonstrable, otherwise this is just  ploy to effectively extend a patent that might otherwise expire.

One of the best blog posts I found that came closest to explaining all this for me in the context of the Gleevec appeal is this post by Derek Lowe who writes about drug discovery and the pharma industry in his blog “In the Pipeline”. In this excellent article we learn that in fact the molecule that is the subject of the Indian patent application/appeal is NOT exactly the same as the molecule that has already been patented in so many other countries. It is a slightly different composition of the active ingredient, one that Novartis indeed claims has greater efficacy and is better for bioavailability and other features. In other words, new and improved.

gleevec CAPSULESOne of the improvements is that the original Imatinib formulation was a capsule whereas the newer formulation is a tablet. They are both taken orally but Novartis Gleevec TABLETSclaims the newer version is just that much better.

But is the “new” drug sufficiently different than the old one to permit a new period of patent protection? The Indian Court said, “no”.

In fact, India has one of the highest bars to clear on this point and they are very stringent about it. Section 3 (d) of the 2005 Indian Patent Act states that new forms or even new uses of existing drugs are not patentable UNLESS they clearly demonstrate a significant increase in efficacy. According to the Bloomberg article already cited above the Court did not find the the “new” Gleevec passed that hurdle:

“Repetitive patent is not permissible on the same drug,” Justices Aftab Alam and Ranjana Prakash Desai said in the court’s ruling in New Delhi. “The drug is neither new nor complies” with provisions of the patent law, they ruled.

Derek Lowe describes these differences in great detail and others more expert will have to decide if this is a new drug or an “evergreening” attempt. Clearly the Indian Court was not buying the argument.

Frankly, neither do I. While I don’t claim expertise, it does seem a bit of a stretch, based on all that I have read, to suggest that the new formulation could be THAT much better than the old one. Given that the original Gleevec was remarkable in just how well it worked, and how few side effects there were (almost as simple as “take a pill, cure a cancer”) it is hard to imagine a new generation of the drug being so dramatically improved.

So that’s it then. Novartis was rebuffed in its attempt to do a sort of patent bait and switch. The new drug is pretty much the same as the old one and the Indian Supreme Court was not buying that it was eligible for a new patent based on the fact that it was pretty much the same as the one already patented.

End of story?

circular argumentWell, not for me, because there was another thing that was nagging at me from the start. And here is where I suspect that Novartis has been caught in a big Catch-22, a circular argument that they couldn’t easily  get out of….

I have not consulted a patent expert, but everything I know about patents (and I am myself a patent holder of two US Patents) says that they are valid ONLY in the country where they are approved. If you want patent protection for your product in multiple jurisdictions, you have to file separate applications for each country. There are some ways to achieve international cooperation and coordination but as far as I understand, a US patent is valid in the US, a Canadian patent is valid only in Canada and so on.

Gleevec is indeed patented in many countries. India is NOT one of them, however.

Let me reiterate that – Novartis does not hold ANY patent on any form of Gleevec whatsoever in India. Novartis themselves confirmed this (see the Novartis press release here).

This is in part due to the fact that the original US (and no doubt other country) patents were filed in 1993. At that time India did not even allow patents on drugs. It has only been since 1995 that India has joined the ranks of the World Trade Organization (WTO) and only since then has it even allowed patents to be held. So Novartis could NOT have even applied for a patent on the original Gleevec at the time it did in so many other countries.

That led me to ponder that if India, like any other country, does not recognize patents issued in other jurisdictions, and if it has not issued a patent on the original Gleevec in any way, how can it now claim that a “repetitive patent is not permissible”. At first I just didn’t see how India can call the Novartis patent repetitive, if there is no legal patent standing in India to be repetitive *of*.

Then after sleeping on it, I realized the trap I fell into. We cannot simply think of the new patent application as as “extension” of an original.This is a new application and stands or falls on its own merits.

One of the mainstays of the patent process is that when applying for a new patent, one must give a full and detailed description of the state of the art as it exists at the time of filing. One of the main tenets of any patent is that it has to be “non-obvious” to someone, as they say, “normally skilled in the art”. In other words, after describing the current sate of affairs, if your invention is deemed to be obvious enough that anyone normally skilled in the art could have thought of it, then the patent will likely not be issued since it does not pass the test of being non-obvious, i.e. it is not really an innovation, not really an “invention”.

So, in 1993 when Novartis was applying for patent protection for the “original” Gleevec all around the world, India was not open for patent business.

In 2006 when Novartis did file for patent protection in India it would have had to cite its own 1993 patents as PRIOR ART, thereby essentially shooting itself in the foot and making any patent on the “original” Gleevec impossible. It is highly doubtful that India would have allowed a filing date to be backdated to 1993 when they did not even allow patents at that time!

In other words, in order to secure any protection at all, I surmise that Novartis HAD to use, as the base of the patent, a different formulation and hope that it was deemed sufficiently different that a new patent would be allowed. It tried and failed….

So there’s the Catch-22. Because they could NOT have applied for a patent in India when they first applied all around the world, they either abandon any hope of any protection in India, or they have to file a new application on a “new and improved” Gleevec since the already filed and allowed worldwide patents on the “original” Gleevec would now become a huge impediment to them in a new jurisdiction many years later.

I am no apologist for Novartis or the pharma industry, but it does seem a bit unfair that if India did not want to play by international patent rules until very recently, that it now essentially invokes those same rules to void this application. Since they were so very late to the party, perhaps some sort of “grand-parenting” allowances might have been considered for patents, like Novartis’ (original) Gleevec patent, that have had worldwide acceptance for years, to be recognized in some way in India.

No doubt such a provision would prove to be unwieldy and ripe for unfair application, but at the same time one has to wonder (or at least I do!) if the denial of this patent application was based as much on protecting India’s powerful and lucrative generic drug industry as much as it was based on sound principles of “obviousness” and protection of Intellectual Property…

 

 

     
 
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Comments

Novartis’ Cancer Drug (Gleevec) vs. the Supreme Court of India: a Classic Catch-22? — 8 Comments

  1. Don’t forget Michael, that the poster-child of precision targetted drugs, Gleevec, is also useful in the treatment of GIST (gastrointestinal stromal tumours) – due to its inhibitory effects on the c-Kit receptor. It also has some activity towards PDGF receptor. The fact is, it works on Bcr-Abl and other tyrosine kinases and that is a good thing. Perhaps overly designing drug specificity might be a bad thing. The second point is that there are now second-line therapies for some of the CML patients who inevitably develop resistance to Gleevec due to point mutations in Bcr-Abl.

  2. The subject of pharmaceutical patent protection has been and will no doubt continue to be debated extensively here in Canada. There are well thought out and valid arguments coming from both sides. The biggest challenge is that the issue cannot be resolved with a nice mold, its simply not a one size fits all matter. It takes alot of expertise of both the science and the legal system. An issue that needs that kind of finesse, expertise and even adroitness from any government evaluation system will have outcomes that occasionally astonish. For those countries that cover the cost of pharmaceuticals (even partially)the financial incentives to carefully scrutinize any new patent protection request are understandable but not always reasonable.

    Good for you for trying to bring some clarity to the public. Not an easy task.

  3. Why is that a surprise? Its the basic rule for the patenting process.

    1993 to 2013 is 20 years, which is more than the maximum life for a patent. Forget about 20, once you publish a research paper, you typically have only 1 year to patent the work. Even if you give a public talk, it becomes prior art. And the prior art is not limited to geography. That’s the first thing your lawyer will tell you once you file an invention disclosure.

    Legally, I don’t think Novartis had a chance. In fact, I would even say, however good the drug be, Novartis is engaging in patent fraud by maintaining the patent on the drug after 20 years. Kudos to the supreme court to call spade a spade!

  4. I think there is a consistent way to see it: stuff from before 1995 is not patented and not patentable and will not be in India.
    I think then your reasoning sounds perfect, they had to try to patent something else, and the discussion was to know if they where crossing the “something else” line.
    But I would think the rejection cause would be prior art (ironically) and not repetitive patententing.

  5. Your post contains some factual errors:

    1. India did have a patentr regime from 1970. But Indian Patent Act 1970, only recognized process patents and not product patents.

    2. India and other developing countries ratified the TRIPS agreement after tough negotiations in 1996 as part of the WTO process. It was then agreed that there will not be any retrospective application of the treaty. So there is no impropriety from India here.

    • Thank you for those clarifications. I was aware of the first but failed to mention that. Thank you.

      I was not aware of the specifics of your second point, so thank you again. That said, I did not intend, nor do I think I did, state or imply any “impropriety” on India’s part. Sorry if it came across that way.

  6. Thanks for very interesting post. Beside what happened in India, it will be interesting to see what will happen in USA and other countries where Novartis has basic patent on Gleevec (the one which could not be filed in India) and that will start expiring in a year time. Will generic companies be able to launch their competitive products or the secondary patent on beta crystalline form of imatinib (which Novartis was trying to patent in India and failed due this order of Indian Supreme Court)will keep on blocking generic competition.

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