New Article – Novartis' glivec battle with India – patentability of pharmaceutical extension patents
Yesterday Novartis
suffered a blow in its battle to obtain Indian patent protection for its beta crystalline form of Glivec (Imatinib mesylate).
The case has attracted a lot of attention (a) because of India’s
unusual section 3(d) which limits patentability and (b) because this is
the first patent to be challenged from the famous mail-box procedure.
Although Novartis’ TRIPS challenge looks like a difficult one to win
before the WTO, there may be some room to move. As I said in my earlier post, India can still play the Compulsory License trump even if Novartis eventually wins patentability for the beta crystalline form.
The article
(which will publish later today) provides background, an update and some strategic options in the
dispute and finishes with a list of online resources for further
reading.
I look forward to your comments.
17 Comments on “New Article – Novartis' glivec battle with India – patentability of pharmaceutical extension patents”
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If India is to comply with the TRIPS agreement as per Section 3 (d), then it is very much obvious that imatinib mesylate (Glivec) has proved to show 30% more bio-availability which IS an enhancement over a known product.
But if exclusivity is given to Novartis, then there are chances that price of the drug will increase and the common man in India who lives below poverty line may not be able to afford the life-saving drug.
Compulsary licensing may be a last option that India may think in favor of Novartis
Thanks Ajay – are you saying that the compulsory license would be in Novartis’ favour as it concedes patentability? (What if India pulled out this option only if it lost the patentability litigation?)Also, its interesting that section 3(d) requires an enhancement ‘of the known efficacy of that substance‘. One of the open questions seems to be whether an increase in bioavailability is actually an increase in efficacy. I’m not sure that it is a simple question (or at least it can certainly be made to be difficult). The IPAB and Courts may also hold that 30% is not sufficient to be an ‘enhancement’ as required by the Act (ie they may say that the minimum improvement must be, say 40%).A problem with this argument would be that it would also exclude enhancements which reduce toxicity (which, again, are presumably not ‘efficacy’ per se). I presume that this wouldn’t stop the Indian Patent Office from making this ruling, though.If the end result is a Compulsory License, then I guess Novartis will be able to say that if they had not fought for patent validity, then they wouldn’t even get the ‘reasonable royalty’ rate which must be awarded under the license.
For those who would like a link to the Article – here it is:http://thinkipstrategy.comarticles/109/
There’s a great discussion going on over at Spicy IP about this case. Here’s my latest response which sets out in more detail some of the issues with the inventive step analogy for the whole of s 3(d):>>>>>>>>>>>>>>>>>>>>>>>>>>>>>Hi Medicherla Ravi Thanks. Sorry – let me clarify.I agree that the bulk of s 3(d) is couched in terms that are analogous to obviousness / lack of inventive step. (I’m
guessing that everyone is in heated agreement about this because the
words of s 3(d) talk about ‘new’ substances etc – ie the section is
saying, notwithstanding that the invention is novel, it is still not
patentable. This makes sense, sure. In some other jurisdictions, it
could be couched as a ‘lack of manner of manufacture’ argument as well
– though this wouldn’t be as useful for India in arguing TRIPS
compliance.)And, of course, a new use for a known substance may
well fail the test for inventive step – if it fits the normal test –
that it would be obvious to a skilled addressee in light of the prior
art.No problem, of course.The point here is that lack
of inventive step requires an assessment of obviousness to the skilled
addressee. There must be some extra property which takes the invention
beyond what would have been obvious.Section 3(d) has three parts, here are the words, broken down into the three parts which are disallowed from patentability:(i)
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;(ii) or the mere discovery of any new property or new use for a known substance (iii)
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.So here’s the problem – Parts (i) and (iii) each
describe an extra property in a proviso which creates the inventive
step analogy – unless you have some enhanced new result or product (or
reactant), it will not be patentable – analagous to obvious.But
part (ii) has no such proviso. It automatically bans any (a) discovery
of a new property (fine – its long been held that they are not
patentable by themselves), or (b) new use for a known substance. There
is nothing which tells us how to cure this. If it is a new use of a
known substance, its all over. This is not the same as stating that
unless you come up with an enhanced result it is not patentable. Let me know what you think.(I’ll co-post this comment on the equivalent post on my site so that readers over there can track it.)
Hi Duncan I am copying my comments on Spicy IP for
you. I hope this sheds some light and the sitaution as it exists today
Section 3 [not merely Section 3(d)] is
that Section 3 covers situations which are inventions but are exceptions as
“inventions not patentable”. I know it is not correct to interpret a section
based upon the title of the Section, but in this case Chapter II is purely
dedicated to “INVENTIONS NOT PATENTABLE” or in other words, that the Act has
demarcated that there are certain inventions cannot be granted patents. Hence
simply put these are exceptions to “patentable inventions” and creation of
statute based upon the prevailing socio-politio-economic conditions of a
country. In fact this is quite obvious to
decipher from Novartis case where the constitutional validity of Section 3(d)
has been challenged since according to Novartis Section 3(d) raises the
patentatibility bar. There are
exceptions such as business methods and computer programme per se which are allowed in several
countries (which means that they are regarded a inventions in these countries)
but are not allowed in India. I hope I am clear on this point. Duncan you are
correct in India new use of a known substance is not patentable nor is the mere
discovery of new form of a known substance unless there is increased efficacy.
This is unique for India. Therefore, Novartis ran into this first road block. To
clear this road block constitutionality was challenged. This is history.
Unfortunately, for Novartis, Ranbaxy and
Natco were able to prove that the increased efficacy is not present since
Novartis themselves have stated that free base form and the salt form compared
with β-crystal form of imatinib mesylate
and the difference in bioavailability is only 30 per cent and also the
difference in bioavailability may be due to the difference in their solubility
in water. Unfortunately again for Novartis they
were not able to show any improvement in the efficacy of the β-crystal form over the known substances rather
was proved that the base can be used equally in the treatment of diseases or
in the preparation of
pharmacological agents wherever the β-crystal is used. The second and more significant problem
that Novartis has run into is that of the imantib mesylate (IM) itself. The
opponents (Ranbaxy and Natco) have
successfully been able to prove that imatinib mesylate salt inherently existed
in the β-crystelline form which is the most stable form of the salt. Even the
affidavit of Novartis in the opposition proceedings states that the β-form is
thermodynamically more stable. Ranbaxy and Natco were able to show through prior
publications and studies done by two reputed government institutions Indian
Institute of Chemical Technology, Hyderabad and Indian Institute of Technology,
Delhi that the salt exists in the β-crystalline form. These experiments were
performed not once but at least ten times and at all times the crystals were
found to exist in the β-form. Hence the invention has been compromised/
anticipated before even the application by Novartis was filed.
This also answers your question that a
comparison of beta-crystalline form with mesylate salt will not be able
to overcome the 3(d) bar. The two steps defined by Novartis that
(i) the imatinib free base has been chemically changed into a salt form (ii) a
particular crystal form of the salt has been made through human intervention and
that this was non-obvious for a person skilled in art nor was it anticipated in
the prior US patent of 1993 (1993 Patent) and was in fact obvious to a skilled
person Once again the opponents were able to
show that “ 1993 patent discloses
methanesulphonic acid as one of the salt forming groups and also the 1993 patent
specification states that the required acid additions salts are obtained in a
customary manner. Further, claims 6 to 23 of the 1993 patent claim a
pharmaceutically acceptable salt of the base compound. The patent term extension
certificate for the 1993 patent issued by the US Patent Office specifically
mentions imatinib mesylate (GleevecR) as the product. All these
points clearly prove that imatinib mesylate is already known from the prior art
publications and the Opponent has satisfactorily proved that the salt normally
exists in the β-form which is the most thermodynamically stable product. Hence I
conclude that the Opponent has succeeded in proving that this invention is
anticipated by prior publication.” There while your points are most
definitely arguable the hitch is that Novartis faces an uphill task to prove the
following “and” conditions: That the invention is not barred by
Section 3(d); and That the compound is novel;
and That it is non-obvious;
and That Novartis did not disclose that the
application was based upon a non-convention country nor did it make any efforts
to change this position. This has been viewed as a misleading tactics. Though
probably this is the weakest of the four, but still will be required to be
proved I have tried to address this based upon
Indian law and practice. I am sure that the above points may not be sufficient
in some other country and Novartis would have a fighting chance. However, in
India these changes are not going to happen in a hurry plus the Indian Patent
Office is quite a stickler of the written words in the Act and not really
interpreting them harmoniously at the moment. Therefore, the question of “new
uses are patentable” would be required to be decided by the WTO Dispute
Resolution and not the Courts of India which scenario Shamnad had predicted long
ago and now has been followed by High Court as well! I hope I have been able through some
light on this issue.
Vaibhav
Hi VaibhavThanks very much – this is great.Ranbaxy and Natco’s involvement – this has not been very widely publicised. Is this just because they were involved in the original opposition when the patent came out of the mailbox but haven’t taken part in the appeals?30% bioavailability possibly due to water solubility. That’s pretty interesting. Are you saying that they used an assay which may have had questionable results (ie – artificially increased bioavailability) due to solubility in water? Or are is it that the technical effect of the crystalline salt is mediated by water solubility? (In which case – this could still be inventive or a 3(d) ‘enhancement’…)No improvement in efficacy of bet acrystalline form over free base – yes, that seems to be a big problem…The mesylate inherently containing the beta crystalline form – now I understand Shamnad’s novelty / inherency point! Aha, another big problem.In light of all of this, the obviousness case is looking better all the time (as you have so clearly spelt out).The new use of known substance point – totally agree that it will be fought out at the WTO. However, there seems to be a pretty good chance that it will be moot as the obviousness case will take care of the claims even if s 3(d) doesn’t.(Unless for some really strange reason, there is disclosure in the specification that would support a new use which is non-obvious and protects the commercial use, and an amendment to claim this is allowed, and Novartis is successful on this point at the WTO, etc…)
Hi Duncan
Thanks for your post and raising of some additional points. Taking a cue from Shamnad, I have tried to address your questions as DB (i.e.) you and my response as VV. Here goes:
DB: Ranbaxy and Natco’s involvement – this has not been very widely publicised. Is this just because they were involved in the original opposition when the patent came out of the mailbox but haven’t taken part in the appeals?
VV: Yes you are correct. Ranbaxy and Natco are the parties directly involved with IPAB and Indian Patent Office. I am not sure if it would be correct to say that they are not involved in the appeal. My guess is that they are indirectly involved in the appeal.
DB: 30% bioavailability possibly due to water solubility. That’s pretty interesting. Are you saying that they used an assay which may have had questionable results (ie – artificially increased bioavailability) due to solubility in water? Or is it that the technical effect of the crystalline salt is mediated by water solubility? (In which case – this could still be inventive or a 3(d) ‘enhancement’…)
VV: From what I can gather is that the water solubility does not change anything in the invention i.e. the efficacy levels are more or less same and the technical effect of crystalline salt is not mediated by water solubility. Hence still the 3(d) bar is not crossed. In any case, the comparison has to be made between efficacy increase between IM and the beta crystalline form of IM not increase in efficacy by water solubility.
DB: The new use of known substance point – totally agree that it will be fought out at the WTO. However, there seems to be a pretty good chance that it will be moot as the obviousness case will take care of the claims even if s 3(d) doesn’t (Unless for some really strange reason, there is disclosure in the specification that would support a new use which is non-obvious and protects the commercial use, and an amendment to claim this is allowed, and Novartis is successful on this point at the WTO, etc…)
VV: Yes, I agree with your reasoning above that it would be more of a moot question now.
It will interest you to know that this case may not even go to WTO Dispute Resolution because in today’s Economic Times (August 8, 2007) Swiss Economic Minister Doris Leuthard has said that the dispute is between a private company and the Indian Judicial system and the Swiss government has nothing to do with it. She is in India to sign a MOU on protection and promotion of IPR. Ms Leuthard has also stated that Switzerland has not experienced any with India’s patent regime yet. “We have not had any problems so far with India’s patent actâ€. There are reports also stating that Novartis will not be moving the Apex Court in India.
Therefore, as I see the situation today, the chapter for Novartis is closed and the discussion on 3(d) will commence once the Indian Government and Indian pharmaceutical lobby deems fit that the Indian industry has reached a level where such bars as 3(d) required to be removed for the progress of Indian economy
Cheers
Vaibhav
Hi VaibhavThanks very much.VV: It will interest you to know that this case may not even go to WTO
Dispute Resolution because in today’s Economic Times (August 8, 2007)
Swiss Economic Minister Doris Leuthard has said that the dispute is
between a private company and the Indian Judicial system and the Swiss
government has nothing to do with it. She is in India to sign a MOU on
protection and promotion of IPR. Ms Leuthard has also stated that
Switzerland has not experienced any with India’s patent regime yet. “We have not had any problems so far with India’s patent actâ€. There are reports also stating that Novartis will not be moving the Apex Court in India. DB: Thanks – this is very interesting news. I wonder whether any other countries might take up the dispute though? Most obvious would be the USA.But, as you say, it seems to be closed, now that Novartis’ home country won’t prosecute the dispute before the WTO. CheersDuncan
Hi Duncan
Do you mean that if a similar situation arises for say a US company, tehre is a good chance that US government will approach WTO??
My take is that US will not do so, because a large number of patents from USA have faced problems and they have overcome them in ingenious ways. Also do not forget that USA has a patent regime which is very different from most of the countries in the world. Therefore, USA may not take it up.
Even otherwise India is fast becoming a country to be looked out for (BRIC countries-Goldman Sach review)and there are too many economic and political reasons for USA to take up an issue against India.
I believe that India is what most of the western world was about 30 to forty years ago. Asia being the next engine from which growth is coming has become an important place to be ignored
Or am i being too optimistic??
comments are welcome
Thanks VaibhavIt’s just that the US obviously has a lot of innovator pharmaceutical companies and the US is not at all shy about proceedings before the WTO.All of those comments also apply to China, and the US was not perturbed about the recent formal complaint to the WTO in relation to counterfeit goods.
From all the fuss about the Glivec case and the criticism of the section 3(d), I’m assuming Novartis has a secured a grant for this invention in other jurisdictions. If so, does anyone know what the published WO, US, EP numbers are?
Reading the exchange Shamnad & Duncan had on SpicyIP, I got the impression that both section 3(d)(i) and 3(d)(ii) are relevant here. Has the Indian Patent Office used both in their argument?
Kind regards,
Anonymous
Yes, Duncan I think you are right. Don’t see why US should have any qualms. I suppose I was getting passionate back then!
cheers
Vaibhav
Hi Anonymous
I have just done a very quick search using free databases and I am pretty sure it is – WO/1999/003854.[I’m not a patent searcher, mind you, I focus on strategy.]
Link to the specification and background at WIPO here.Link to patent family at Patent Lens here.
It’s been granted in a few countries already – two granted US patents, for example.
Yes, the specification discloses uses of the beta crystalline form of the mesylate salt of imatinib.
For the second part of 3(d) to apply in a useful way for Novartis, the questions to consider are whether any of these uses are ‘New Uses of a Known Substance’ and then secondly, are any of these commercially worth protecting. (Given that Use patents are not as useful at provising a monopoly because a generic can simply delete that use from the PI leaflet.)
Indian Patent Office didn’t have to use either 3d(i) or 3d(ii) [this is my nomenclature, bu the way, not in the Act], because the High Court simply dismissed the proceedings saying that it was competent to hear the action.
Thanks Vaibhav
So, who wants to pull down the USPTO and EPO filewrappers to see how Novartis avoided / is avoiding obviousness objections elsewhere?
Dear Duncan,Your post has generated some very interesting discussion. Just a couple of quick points:1. I think you’re absolutely right in pointing us to the US/EU applications and finding out how Novartis managed to cross the non obviousness bar there. I havent personally seen any of these documents-but would love to. So if you receive any feedback on this, please let me know.2. Ranbaxy and Hetero are involved in the appeal. In fact, Ranbaxy’s lawyer, Mr Lakshmikumaran has been the best of all the counsels who performed at the Madras High Court recently.3. It’d be interesting to ask why Novartis did not patent “Imatinib Mesylate” or claim this separately–did they know it was “obvious” from the 1993 application.4. Evidence was offered by Ranbaxy and others that the Beta Crystalline (BC) form of IM inhers in IM and comes up anytime you produce IM. Novartis strongly objected stating that the initial sample used to test this was contaminated with the BC form–and hence you had BC. I’m not sure who is right–and look forward to a ruling from the IPAB on this.
Hi ShamnadThanks for your comments.”3.
It’d be interesting to ask why Novartis did not patent “Imatinib
Mesylate” or claim this separately–did they know it was “obvious” from
the 1993 application.”I think your suspicion may be correct.”4. Evidence was offered by Ranbaxy and others that the Beta Crystalline
(BC) form of IM inhers in IM and comes up anytime you produce IM. Novartis strongly objected stating that the
initial sample used to test this was contaminated with the BC form–and
hence you had BC. “That’s the funny thing about experiments in patent cases – they can cause lengthy delays and diversions. So, they can be deployed strategically, depending on what you’re trying to do.I once was involved in a patent infringement case that went for 10 years – even at the end (when it was settled) the parties were still arguing over the experiments.On the one hand, one could wonder whether it would have been better for Ranbaxy and the others to keep their powder dry on this point. The documentary disclosure seems pretty compelling alone.However, I’m not sure what Novartis could achieve by a length delay – except time to fully test a WTO dispute…