Posted by Derek April 1, 2013This story is all over the news today, but it's my impression that most of the stories leave out crucial details. This is not just a big multinational drug company being put in its place by Indian courts, nor is it some crazy ruling with no basis in fact. Here's the story, as best I understand it.Novartis has never had a patent for imatinib (Glivec/Gleevec) in India. I'm not completely sure why that is, but I would think it's because that back when the compound was being developed was the era when Indian drug patents did not exist. As the country has entered the WTO, it's had to comply with the world's intellectual property framework, and it's safe the say that the dust has not yet settled from this process.So when Novartis filed for an imatinib patent in India, it was for a different polymorph of the drug, which they hoped would be patentable chemical matter. The Indian patent office disagreed in 2006, saying that this was merely a reformulation of an existing compound (which had been approved in the US back in 2001), and rejected the application. Novartis has been appealing that decision through the Indian court system ever since, and this latest ruling is the last, from the Indian Supreme Court. As the court's decision says: In the application it claimed that the invented product, the beta crystal form of Imatinib Mesylate, has (i) more beneficial flow properties: (ii) better thermodynamic stability; and (iii) lower hygroscopicity than the alpha crystal form of Imatinib Mesylate. It further claimed that the aforesaid properties makes the invented product "new" (and superior!) as it "stores better and is easier to process"; has "better processability of themethanesulfonic acid addition salt of a compound of formula I", and has a "further advantage for processing and storing." Novartis, for its part, feels that they have been done in by one particular section of Indian patent law, section 3(d). This was put in to prevent companies from "evergreening" their drug patent estates, and it requires proof of enhanced efficacy for new forms of existing compounds in order for them to be patentable. (That's as opposed to the situation in most other patent regimes, where once you've shown that you have a new substance, the uses you already knew about for its earlier form are enough to establish utility, to go along with the novelty). Here's Novartis' take: Glivec has been awarded patents in nearly 40 other countries, including China, Russia and Taiwan, but the IPAB is denying one for India. The IPAB acknowledges that Glivec satisfies the international requirements for novelty and inventiveness, but it does not find Glivec to meet the requirement under Section 3(d) of the Indian Patents Act of 2005. This act introduced a new efficacy enhancement hurdle for patenting new forms of known compounds. We believe that Section 3(d), the Indian legal paragraph intended as a hurdle for evergreening, should not be applicable to the breakthrough medicine Glivec, which has changed the lives of patients with rare cancers. The misconception regarding the innovation of Glivec is based on a patent that was granted in 1993 (not in India) for the synthesis of the molecule imatinib. This molecule, without further development, could not safely be administered to patients and represented only the first step in the process to develop Glivec as a viable treatment for cancer. We selected the mesylate salt of imatinib and then developed the beta crystal form of imatinib mesylate to make it suitable for patients to take in a pill form that would deliver consistent, safe and effective levels of medicine.Novartis claimed that the increased bioavailability qualified as increased efficacy, but the opposing argument was that therapeutically, the two compound forms were never shown to be differentiated. The Indian Supreme Court, in fact, noted in its decision that Novartis had never provided any data on the effect of bioavailability on therapeutic efficacy, with the implication being, I think, that if they had such data they surely would have presented it by now in order to strengthen their case. The court had this to say about the beta-crystalline form: It is seen above that in the US the drug Gleevec came to the market in 2001. It is beyond doubt that what was marketed then was Imatinib Mesylate and not the subject product, Imatinib Mesylate in beta crystal form. It is also seen above that even while the appellant's application for grant of patent lay in the "mailbox" awaiting amendments in the law of patent in India, the appellant was granted Exclusive Marketing Rights on November 10,2003, following which Gleevec was marketed in India as well. On its package, the drug was described as "Imatinib Mesylate Tablets 100 mg" and it was further stated that "each film coated tablet contains: 100 mg Imatinib (as Mesylate)". On the package there is no reference at all to Imatinib Mesylate in beta crystalline form. What appears, therefore, is that what was sold as Gleevec was Imatinib Mesylate and not the subject product, the beta crystalline form of Imatinib Mesylate. I'm of two minds about that argument. The packaging often does not describe individual polymorphs of compounds - both the original form of imatinib and the beta-crystalline form are properly described as "imatinib mesylate". At the same time, it does appear that the drug has been administered as the earlier form for some time. So the Indian court affirms their section 3(d), which is a high bar, but they do say that it should be one that is clearable in practice: We have held that the subject product, the beta crystalline form of Imatinib Mesylate, does not qualify the test of Section 3(d) of the Act but that is not to say that Section 3(d) bars patent protection for all incremental inventions of chemical and pharmaceutical substances. It will be a grave mistake to read this judgment to mean that section 3(d) was amended with the intent to undo the fundamental change brought in the patent regime by deletion of section 5 from the Parent Act. That is not said in this judgment." We'll have to see how this works out in practice. India has a right, of course, to set its patent laws out in this way, but will it always work out like this when a section 3(d) issue comes up again? Or will that only be when it's a multinational company selling an expensive drug? Pricing, in fact, is not supposed to enter into this dispute, although for a while, it looked as if it would. The Indian appellate board, as Spicy IP reports, had originally tried to being in another interesting part of the patent law, section 3(b), which forbids patents for inventions that "offend public order or morality". They had tried the argument that Novartis' pricing offended public morality, but the Indian Supreme Court, to their credit, declined to pursue that line of thought.So this case is not the end of drug patents in India. It's not supposed to be some mighty victory for the generic drug makers there, either, although I'm sure they're happy with it. (I might note that all the preening in the Indian press about the country being the "pharmacy to the world" would be more justified if any of the drugs being made had actually been discovered in India, through the ingenuity of Indian drug companies, risking Indian capital and shareholders' money. But they weren't).What it does mean is that Indian drug patent law has gone from being nonexistent a few years ago, to being one of the strictest around. I hope that it's applied uniformly. Novartis has lost what was not a very strong case, to be honest, but the courts in India will hear stronger at some point.
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