Guest Post by Srividhya Ragavan (Professor of Law, University of Oklahoma College of Law)
The Indian Supreme Court’s verdict on the Novartis patent application has garnered a lot of attention as having set a stringent standard of nonobviousness for patents. In India, this litigation is pitched as a battle between big pharma and health aid groups.
This recent saga at the Supreme Court relates to a patent application that was originally filed in 1998 for a cancer drug named Gleevec (or Glivec, in Europe). Gleevec is the beta crystalline form of imatinib mesylate, which is the salt form of the free base and is used to treat chronic myeloid leukemia, a form of cancer. This application in India claimed priority from an earlier application filed in July 1997 in Switzerland. The application was opposed in India on the basis that imatinib mesylate was anticipated by the earlier Novartis US patent No. 5521184. As a side note, Novartis’s US application for the free base of Imatinib -which was the crystalline form —issued as a patent in the United States in 1996 owing to a 1993 filing date. When after losing the mail-box dispute, India opened its doors to a transitional mail-box application facility, Novartis filed a patent application in India in 1996. Overall, Novartis had over 35 patents over this polymorphic form of Gleevec in different countries. The application was reviewed in India in 2006 once India fully transitioned into a patent regime as required under the TRIPS agreement. Notably, even before the application was taken up by the patent office there were 5 pre-grant oppositions filed against the application!
In gist, the argument against Gleevec in India was that this application related to new form of a known substance. In pharmaceutical chemistry, a different crystalline form of the same chemical substance is called a polymorph, the patenting of which is specifically prohibited under § 3(d) in India unless it also results in enhanced efficacy. Now, § 3(d) of the Indian patent statute, the operative section reads as follows:
3. What are not inventions. – The following are not inventions within the meaning of this Act,
…
(d). 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.
Explanation.—For the purposes of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy;
In gist, India does not allow the patenting of new forms of known substances unless it also results in enhanced efficacy. The assertion in India was that the salt form for which the patent application was filed inherently existed in the original crystalline form. Considering the US patent as a prior art, the Patent Controller concluded that the application was obvious for covering a new form of a known substance under § 3(d) of the Patents (Amendment) Act of 2005.
Soon Novartis pursued an appeal to the High Court of Chennai on the grounds that § 3(d) was unconstitutional and in violation of India’s obligations under TRIPS. The Chennai High Court established that § 3(d) was indeed Constitutional and within the scope of the TRIPS agreement based on the fact that the section deals with all technologies and does not limit itself to pharmaceutical innovations. The explanation to the section becomes applicable to pharmacology inventions and works to strengthen the understanding of the overarching test. The test, the court explained cast a duty on the patent applicant to prove that the discovery had resulted “enhancement of a known efficacy of that substance.” The court added that the explanation creates a “deeming fiction that all derivatives of a known substance would be deemed to be the same substance unless it differs significantly in properties with regard to efficacy.” Thus, was born the higher standard of nonobviousness that India has embraced with such vigor. In its opinion, the Chennai High Court agreed with the patent office that Gleevec was an obvious improvement and that the applicant should prove enhanced efficacy by showing enhanced therapeutic efficacy in order to get a patent. Interestingly, Novartis filed another patent application for the alpha version of the same compound; that application was also denied.
It was during this time that the government of India issued a notification constituting the Intellectual Property Appellate Board (IPAB), which is a tribunal with judicial powers under which all patent appeals were transferred. It is important though to understand that, despite being a tribunal, the IPAB’s judicial pronouncements have gained in reputation and stature over the years. Eventually, the Novartis patent application, like the other patent appeals, landed in the hands of the newly constituted IPAB on transfer from the High Court. The IPAB alluded to the original 1993 Zimmerman Patent facilitated the formation of imatinib mesylate salt by reaction with “aliphatic sulfonic acids, such as methane -,ethane – or – 2-hydroxy ethane -sulfonic acid.” Interestingly, the IPAB clarified when nonobviousness is evaluated for a pharmaceutically active substance, in particular, the application material would finally have to be evaluated to determine whether the compositions fall within the category of “not an invention under § 3(d) of the Act.” This evaluation determined whether the new form/derivative of a known substance displayed significant enhancement in properties with regard to efficacy. Thus, the IPAB gave the impression that the § 3(d) analysis is tied to nonobviousness and not patent eligibility. In considering Gleevec, the IPAB held that the increased bioavailability of the salt of imatinib (application material) and the increased solubility did not result in increased efficacy.
Novartis preferred an appeal to the Supreme Court in 2009, the same year that the IPAB upheld the rejection of Gleevec by the Controller. The Supreme Court considered whether an invention that clears all of the requirements for an invention can be denied on the ground that § 3(d) puts it out of the category of “invention”? The manner of phrasing the question in itself suggests that § 3 is not a threshold question in India. That is, one gets the feeling that whether an application material falls within the category excluded under § 3 is determined only for inventions that cross the § 2 requirements of utility, novelty and nonobviousness. This view is further bolstered by the statement elsewhere by the Supreme Court that “in case of chemicals and especially pharmaceuticals … [of] a new form of a known substance with known efficacy, [] the subject product must pass, in addition to clauses (j) and (ja) of section 2(1), the test of enhanced efficacy as provided in section 3(d) read with its explanation.” That said, elsewhere the court, in denying that § 3 is not a provision ex majore cautela, adds that the vital distinction is between the concepts of invention and patentability. So, the conclusion perhaps is that § 3 is akin to patentability question although in practice in India, it is tagged with the nonobviousness question.
As for the specific constituents of the § 3(d) requirements, the Supreme Court clarified that the term efficacy relates to “therapeutic efficacy.” The court then went on to discuss the test or parameters for providing such efficacy noting that such proof shall be weighed on strict and narrow standards. In the case of pharmaceutical compounds, the Court noted external and internal factors should clearly demonstrate therapeutic efficacy and it should be specifically claimed and established by research data. Thus, “the mere change of form with properties inherent to that form would not qualify as “enhancement of efficacy” of a known substance.”
As for the patent itself, the court adopted a stance similar to the Controller of patents and the IPAB to hold that imatinib mesylate is represented entirely by the Zimmermann patent. It added that after the Zimmermann patent issued, Novartis applied for, and obtained patents on different forms of the substance. But, no application was made on imatinib mesylate on the non-crystalline form. The court concluded that it is because imatinib mesylate is fully a part of the Zimmermann patent and does not call for a separate patent and thus, denied the patent.
Notably, the interest and role of non-governmental organizations in India in access issues as far as intellectual property is concerned is remarkable and distinguished. Further, the country’s interest in hearing and dispensing intellectual property issues has also become notable. The Novartis litigation has showcased India’s interest and ability as far as pharmaceutical patents are concerned. This case reinforces the suspicions for the need of a higher bar to get a patent issued in India. It also proves that the power of lobby groups notwithstanding, businesses needs a dose of local reality especially in countries in India. It must take exceptionally bad market assessment to sell a drug for approximately $ 2400 for a month’s supply (against a cost of $ 160 for the same from a generic manufacturer) in a country where the per capita income is estimated at a low $ 1 to $ 10 per month for a vast majority of the population. To give a perspective, an Indian employee who earns $ 2400 per month would consider himself very well-employed. In fact, in the lower middle class (forming about 300 to 400 million people), one would be considered agreeably employed if they earned $ 2400 in a year. And, big pharma cannot hope to erase away this ground reality with its lobby power.
Look who is still running.
Ready yet…
Let the record show that Malcolm has (once again) turned tail and run away, after belittling someone else.
The hypocrite has no courage at all. Typical internet tough-guy.
Ready yet…
Why would docs prescribe a form of an already available drug, which form has been determined not to be more efficacious than the already available drug?
I don’t know how things work in India, but the answer here is pretty simple, and two-pronged: (1)Marketing, and (2)Time Pressure. Doctors frequently prescribe exactly the drugs that their patients ask for, and doctors don’t have or take the time to analyze whether that new blood pressure medication with the fancy name is actually any better than the therapies that have been around for decades (and that are off-patent). They prescribe the one that the attractive young pharmaceutical sales rep just told them about (with free samples!).
link to plosmedicine.org
there mu$t be $ome idea$ a$ to why thi$ i$ $o.
Does anyone see an inconsistency here:
Imantinib is already available and patented under Zimmerman. Novartis was denied a patent on a crystalline form of imantinib mesylate because “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” is not patentable.
So here’s the rub: Why would docs prescribe a form of an already available drug, which form has been determined not to be more efficacious than the already available drug? Any help in correcting my logic is appreciated.
I am annoyed with Annoyed.
Not because he is attempting to distinguish an argument of emotionalism by Greg Wu, but because he is not doing so effectively.
I reach out to Greg Wu and empathize with his suffering and his battle. Godspeed.
I would then turn around and hope that Greg Wu understands that the rules of the game were in place before Novartis set out to even develop and put Gleevec on the market, and that his angst concerning Novartis’ actions in fully legally and ethically protecting its intellectual property are simply misplaced.
Another (albeit different) example of shooting arrows at the wrong target.
How much do you think their drug is worth? More or less than a luxury car? Or are you demanding discounts from BMW and Ferrari too because you don’t understand how they can charge that much for their cars.
Wow – Greg is buying a luxury car every year, and he has the nerve to be concerned about people dying in India? Thanks for setting him straight, Annoyed!
If your life is not worth paying $72,000 to maintain then just stop buying the drug if you don’t think Novartis’s drug gives value for money.
Why shouldn’t they charge that much for a life saving drug? Is it because Novartis was responsible for your disease?
How much do you think their drug is worth? More or less than a luxury car? Or are you demanding discounts from BMW and Ferrari too because you don’t understand how they can charge that much for their cars.
If it is “meant to prevent the practice of evergreening” in pharmaceuticals by implementing heightened standards for patentability applicable essentially only to pharmaceuticals, that is precisely the kind of discrimination that the TRIPS provision, that India has agreed to, is meant to prevent. Of course, India has a strong generics industry which is why it is openly hostile to pharmaceutical patenting and why it is openly violating its obligations under TRIPS.
Ready yet…
(Malcolm must be,
wait
.
wait
.
(looking the other way)
Ready yet…
Ready yet…
I’m an American suffering from an intestinal cancer called GIST that is treated by 400mg of Gleevec daily for three years. My insurance plan is billed $6000 per 30 day supply of the drug. Mortality from my disease when treated with Gleevec is less than 10% after ten years but without Gleevec is 50% at 3 years. Gleevec has done a lot for me just by giving me hope.
It is difficult for me to understand how Novartis can charge that amount for a drug that is 15 years old that others can supply at a small fraction of their price. India’s decision appears to be both lawful and right.
Ready yet…
Nice vacuous comment Malcolm.
Atta boy, you continue to unimpress.
LOL – I have no idea what you are talking about Malcolm.
What is a pro-polymorph patent zealot?
B-b-b-b-because the structure has been changed.
In fact, the prima facie obviousness of the polymorphs is often recognized. The claims are granted (rightly or wrongly) because of “unexpected results.”
Nice try, though, anon. You almost “devastated” all those pro-polymorph patent zealots in your imaginary universe. Maybe next time?
it is you that needs to clarify.
HUMPTY HAS SPOKEN!!! BOW DOWN!!!!!!
Good point on 27(2).
Not so good point on sueing the competitors.
In US patents are exploited much to sue the competitors…..it’s not the case in India
India has made full use of the Article 27(2) of TRIPS and I don’t find section 3(d) of Indian patent law violating the TRIPS agreement
In US patents are exploited much to sue the competitors…..it’s not the case in India
India has made full use of the Article 27(2) of TRIPS and I don’t find section 3(d) of Indian patent violating the TRIPS agreement
How do you not understand the question? Your post at 6:50 was in reply to me. I am asking you to explain how your post in reply to me touches what I say.
You claim not to be able to have a conversation, turn and blame me, when it is you that needs to clarify.
Please. Do.
Your question at 8:31 was:
“Why do you think that I am claiming that a functional patent system would not have an ‘obviousness’ requirement?”
The “distinction” you made at 6:29 was:
“The barrier in the US is distinctly different: “enhanced” is not strictly required.
Innovation does not color only between the lines. It is not linear. That is why in the US patents for inferior products or methods are allowed. What this does is expand the breadth of knowledge, the possibility of ever more connections. Even “dead ends” can be worthwhile.
As to whether this is ‘noise’ or not, I do not venture to put such a label. Rather, I think it in line with Jefferson and Lincoln, a liberal encouragement and the fuel of interest.”
I do not understand the question and I do not see the distinction. So, a conversation with you is still not possible.
Sounds like a Crybaby Veto to me – should we look back to see your earlier admissions of just what criteria you actually use?
(and I note the telling phrase above: “I provoke it” – conversation is not “provoked.” Yes, you attempt to provoke, and at the same time endlessly shill about the EP. But when a clarification is needed, or a point in rebuttal is offered, you vanish.
Conversation just is not as one-sided as you chose it to be. In this instance, you seem to want to attribute some message about obviousness to me which comes from nowhere. Why is that? And please, don’t hide behind the curtain of “incomprehensible English,” that ploy does not work for Malcolm, and it is easily seen as a smokescreen here.
So tell me explicitly, whyam I plain wrong here. Answer my question of 8:31, and address the distinction I make at 6:29, and please, no false attributions to a view on obviousness.
Plain wrong, anon. Very interested in a meaningful conversation with the readership in general. I provoke it as best I can. Specifically with you though, I have tried many times, and each time failed. I think it has something to do with your bizarre thinking and inability to write in comprehensible English. It is that which turns me off. As here.
Ready yet…
Just as I thought – not interested in an actual conversation.
Lovely soapbox there MaxDrei.
Ready yet…
“Just because the USPTO is so often duped into allowing claims to blatantly obvious polymorphs so that drug companies can get patents”
B-b-b-b-because the structure has been changed.
Isn’t it common that, having mentioned the base compound in a patent, you automatically state that the patent also covers “salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives” of the base compound? Isn’t that because it is so freaking obvious.
So what is the controversy with a statute that makes that clear? Just because the USPTO is so often duped into allowing claims to blatantly obvious polymorphs so that drug companies can get patents, why is it noteworthy or controversial that other patent offices refuse to be duped?
Going further than India does, I would nix the possibility of getting a patent issues based on enhanced efficacy, or even surprising or synergistic effect. It is obvious to try, with good expectation that it will work, every conceivable polymorph. It is just a matter of getting around to it. Why grant a patent for discovering that something works based on your understanding that it probably will work because you know a closely related compound will work.
Perhaps a question then that you might “feel interested” in answering:
Why do you think that I am claiming that a functional patent system would not have an ‘obviousness’ requirement?
You seem to have taken my 6:29 AM post as indicating such (that, or you are just throwing out a strawman with your reply to that post).
Why ask me when you yourself are such a sophisticated user of the English language? Like you though, I don’t know anywhere where surprising and enhanced are synonymous.
But (in line with that level of sophistication) your question I now realise is intended to be rhetorical (and so requires no answer).
“Surprising” is not the same as “enhanced,” is it?
Obviousness is one thing in engineering and quite another in chemistry. The EPO obsession with comparative data does not extend to machines. When I claim an apparatus I will not have to provide the EPO with data that shows the machine (say, a gearbox) to be superior. Inferior gearboxes can be even more unobvious.
But if the state of the art includes Molecule X and its salts, and my claim is to (say) the sulphate of X, that claimed subject matter is obvious (everywhere on Earth) unless the sulphate delivers a surprising effect.
Name me a functioning patent jurisdiction, anon, just one, effective to promote science and useful arts, where this obviousness landscape is not present.
The barrier in the US is distinctly different: “enhanced” is not strictly required.
Innovation does not color only between the lines. It is not linear. That is why in the US patents for inferior products or methods are allowed. What this does is expand the breadth of knowledge, the possibility of ever more connections. Even “dead ends” can be worthwhile.
As to whether this is ‘noise’ or not, I do not venture to put such a label. Rather, I think it in line with Jefferson and Lincoln, a liberal encouragement and the fuel of interest.
For someone who is living on less than $150pm it may not make much of a difference, but there are many people in India, who live between these two extremes. And Indian Generic Industry had not being supplying essential medicines only for Indians. Many of the Least Developed Countries are depending on Indian generic drug industry to meet their medical requirements. India is called the pharmacy of the world for this specific reason and it is a request that this judgment should not be understood in isolation, as it is not. The Supreme Court of India had given this verdict keeping in mind many factors including the strive made by countries like India, Brazil and other LDCs at the WTO Doha summit to modify TRIPS conditions to be public health friendly.
Section 3(d) of the Indian Patent Act specifically is meant to prevent the practice of evergreening. Anon points out that “S.3d prohibits patenting … even when the invention meets the requirements of novelty, inventive step and industrial applicability”. But if the claimed invention is not satisfying the condition of efficacy, it is not satisfying the requirement of inventive step. It has become a regular practice for the Pharma, to make trivial changes in their existing patents and make new patent claims, just for extending the monopoly they enjoyed for 20 long years.It was to prevent this practice the Indian Legislature had added S 3(d).
At the heart of this Decision is the point that:
“India does not allow the patenting of new forms of known substances unless it also results in enhanced efficacy”
which for me does not render India a pariah State if only because Applicants at the EPO are faced with much the same barrier to validity. Application liable to be refused unless Applicant comes up with comparative data that evidence a surprisingly good result.
The rest of any commentary on the case is just noise, isn’t it?
Ms Ragavan is right that the IPAB referred to an argument of one of the counsel that Sec 3(d) is effectively a higher standard of obviousness incorporated into the statute. This was the argument was originally made by one of the intervenors before the Madras High Court in the context of the challenge to the constitutional validity of Sec 3(d) to contend that there was nothing arbitrary or unreasonable about it. This argument was repeated in the proceedings before the IPAB by the same counsel, though it was irrelevant in the context of the Novartis’ appeal against the refusal of its patent for imatinib mesylate.
As Ms Ragavan rightly notes, Sec 3(d) is a separate and distinct provision relevant only when the subject matter is a new form of a known substance (usually a chemical). The new form can be novel and non-obvious, but it will nevertheless be denied a patent if it does not have enhanced efficacy.
The objective of this provision is to prevent delay of generic entry, which is a fraught question for pharmaceuticals and agrochemicals. The implication is that while the ‘basic’ patent will be granted in India, a subsequent patent for a new form (polymorph, pure form, etc)which very often additionally covers the product on the market will not be granted unless there is an enhancement of efficacy. In the case of Gleevec, the polymorph patent extended the patent monopoly by about 5 years in the US – that is the extension that India wants to avoid, unless there is a corresponding benefit to society in terms of enhanced efficacy.
I think the last paragraph of this article is a red herring.
Although public health considerations have undoubtedly played a role in the formulation of the present version of the Indian Patents Act, they are not at the basis of the decision of the Supreme Court, which essentially deals with technical and legal considerations. The threshold set by the Supreme Court for inventive step does not appear to me intrinsically hostile to the pharmaceutical industry, but it IS arguably higher than in other jurisdictions. I don’t see a problem with that, since it is within India’s discretion as a sovereign nation to decide where to put the bar for its patents.
How does selling a generic copy for $180 per month help a poor person in India? For someone who has to live on less than $150 per month it makes no difference if some drug is sold for $180 or $2,600; it’s equally unaffordable. Apparently Novartis has been supplying 60,000 indigent Indian patients with free Gilvec. Have the Indian generics been doing the same? Looking beyond the poor, there are many millions of people in India whose affluence (and private health insurance coverage) exceeds that of average Americans, but who don’t want to pay for innovation. Isn’t that part of “local reality” too?
“cheerleader… was spoonfed a lot of reality… but he spit it up every time”
Reminds me (a lot) of you Malcolm.
Ready yet to provide the answer to the simple question (Myriad) as to how to differentiate something from nature’s warehouse from something effectively the same as in a claim?
As for the specific constituents of the § 3(d) requirements, the Supreme Court clarified that the term efficacy relates to “therapeutic efficacy.” The court then went on to discuss the test or parameters for providing such efficacy noting that such proof shall be weighed on strict and narrow standards. In the case of pharmaceutical compounds, the Court noted external and internal factors should clearly demonstrate therapeutic efficacy and it should be specifically claimed and established by research data.
Sounds like a reasonable policy.
It must take exceptionally bad market assessment to sell a drug for approximately $ 2400 for a month’s supply (against a cost of $ 160 for the same from a generic manufacturer) in a country where the per capita income is estimated at a low $ 1 to $ 10 per month for a vast majority of the population. To give a perspective, an Indian employee who earns $ 2400 per month would consider himself very well-employed. In fact, in the lower middle class (forming about 300 to 400 million people), one would be considered agreeably employed if they earned $ 2400 in a year. And, big pharma cannot hope to erase away this ground reality with its lobby power.
Indeed. Big pharma could use a dose of “local reality” pretty much everywhere on earth. But they don’t like the taste of it. For example, Big Pharma cheerleader Kevin Noonan was spoonfed a lot of reality in the years preceding the Prometheus case but he spit it up every time.
1) The “covered business method patents” includes non-method claims (the term “covered business method patent” means a patent that claims a method or corresponding apparatus).
2) The (circularly-defined) caveat included in the law: (that the term does not include patents for technological inventions).
Doesn’t the U.S. patent statute and courts apply different laws/rulings to different fields of technologies and different classes of inventions, and thus also in violation of TRIPS, for years if not decades? For example, the line of cases analyzing the “predicatable results” standard is different for pharma than it is for other technologies. More recent examples are that all “tax strategies” are deemed within the prior art, and “covered business method patents” are, in hindsight, suspect.
“inherently existed in the original crystalline form”
Sounds like the new form is not different in kind from the previous form.
The Indian Section 3(d) clearly violates the TRIPS prohibition of discrimination between different fields of technology in their patent regimes. Section 3d does not apply to all technologies – the prohibition on paenting 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” (even when the invention meets the requirements of novelty, inventive step and industrial applicability), clearly only targets chemical and pharmaceutical inventions.
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