Friday, June 13, 2008

DAF-K Award Winning Essay

Imatinib mesilate – the controversy surrounding it
Dr. Ananya Datta
Postgraduate Trainee – Department of Pharmacology
Institute of Postgraduate Medical Education & Research (IPGME&R)
244B Acharya J. C. Bose Road, Kolkata – 700020


Introduction
Imatinib mesilate is an anticancer medicine with a novel mode of action that is indicated in chronic myeloid leukemia and acute lymphoblastic leukemia, two of the most prevalent forms of blood cancer, and in certain other malignancies such as gastrointestinal stromal tumors and dermatofibrosarcoma protuberans. It is a potent and specific inhibitor of the enzyme tyrosine kinase which is involved in malignant proliferation of tumor cells in many cancers. In chronic myeloid leukemia it is recommended as first-line treatment if the cancer is Philadelphia chromosome positive and also offers the possibility of rescuing patients who have failed previous chemotherapy. The drug is given orally and lacks the typical adverse drug reactions of cytotoxic anticancer drugs. Imatinib is the first drug in its class to be licensed for use and has possibly brought about a major therapeutic advance in the treatment of malignancies because of its novel mode of action. Treatment with the drug may be continued as long as there is no evidence of progressive disease or unacceptable toxicity.

The controversy
Imatinib is produced and marketed internationally by the Swiss multinational pharmaceutical manufacturer Novartis. Novartis markets imatinib worldwide with the brand name GLEEVEC in the United States of America (US) and GLIVEC outside of the US. In India, Novartis’ product costs approximately Rs. 1,20,000 (US$ 3000) per patient per month. Various Indian manufacturers, such as Cipla, Hetero and Ranbaxy, have commenced manufacture of imatinib and generic versions of the drug are priced at about Rs. 8,000 (US$ 200) per patient per month in the Indian market. Such a huge difference in cost of a potentially life-saving drug, the treatment with which has to be continued indefinitely, is a matter of grave concern and obviously, the innovator brand would be unaffordable and therefore inaccessible to the majority of Indian patients.

The compound imatinib mesilate – in its alpha and beta crystalline forms as well as the amorphous substance – has been known since prior to 1995 and its use for treatment of blood cancer was approved by the Food & Drug Administration (FDA) in the US in 2001. Separate patents covering the original compound (which would also include all its forms) were claimed and granted in several countries during 1992-1995 but were not claimed by Novartis in India, probably because under the Indian Patent Act of 1970, only process patents were allowed.

In 1998, Novartis filed an application in the Chennai Patent Office for a patent on imatinib mesilate (GLIVEC). At that time, India still did not grant patents on pharmaceutical products, but in November 2003, Novartis was able to obtain exclusive marketing rights (EMR) on GLIVEC for a period of five years, based on a temporary provision of the Patent Act which was undergoing amendments to comply with the requirements of the Trade-Related Aspects of Intellectual Property (TRIPS) agreement to which India was a signatory. The granting of EMR was a TRIPS obligation for countries like India, which did not grant patents for pharmaceutical products before 2005. The EMR operated like a patent monopoly, preventing seven of nine Indian pharmaceutical companies from producing affordable generic versions of imatinib mesilate. They were forced to withdraw the production and sale of generic versions of the drug in India and other developing countries.

In 2005, India made its patent law fully TRIPS-compliant and Novartis’ patent application on GLIVEC came up for examination by the Chennai Patent Office. The Indian Patent Act allows for any person or group to oppose a patent application before it is granted. When Novartis restrained Indian companies from marketing generic versions of GLIVEC, the Cancer Patients Aid Association (CPAA) filed a pre-grant opposition on behalf of cancer patients in the Chennai Patent Office. In addition to the fact that CPAA, who were purchasing generic versions of the drug, found it very difficult to support treatment of its patients due to the high cost and limited availability of GLIVEC, there was also a technical ground for CPAA’s opposition in that Novartis was attempting to patent a particular form (beta crystalline form) of imatinib mesilate which is not a novel drug that satisfies patentability standards.

In January 2006, the Chennai Patent Office rejected Novartis’ patent application on the ground that the application pertained only to a ‘new form of a known substance’. This decision brought relief to numerous cancer patients as it not only prevented a patent monopoly till 2018, but also automatically cancelled the EMR.

Background to the controversy
Many decades ago, India took the conscious decision to restrict monopoly rights in the field of pharmaceuticals by recognizing only 'process patents'. Under the Patent Act of 1970, product patents were not recognized and pharmaceutical companies were free to devise a non-infringing process of manufacturing a drug even if the same was protected by a process patent in India. This situation changed when India agreed to switch over to the product patent regime by becoming a member of the World Trade Organization (WTO) which worked out the TRIPS agreement. This required every member country to provide product patent protection for pharmaceuticals. Though India became a member of the WTO in 1995, as a developing nation, it was given a 10-year transition period to fulfil the obligations of TRIPS by amending its patent law to effect the change from process patents to product patents regime, along with a 20-year patentability period.

While this is accepted, debate pertains to the standard of patentability under the amended Indian Patent Act. TRIPS, as a minimum standards agreement, requires WTO members to grant patents for inventions in all fields of technology for a period of 20 years if they satisfy the universally accepted criteria of patentability. The first notable external interference with the Indian patent law came when the US and European Union filed a complaint against India before the WTO dispute settlement panel alleging that it had not complied with its obligations under TRIPS. That case was decided against India and the Patent Act had to be amended to introduce provisions for accepting patent applications through an advance 'mailbox' arrangement (to be opened and examined in 2005) and for granting an interim patent-like monopoly right, termed EMR, in certain cases, pending consideration of the patent application.

The time that Novartis chose to enter India with GLIVEC was a period in which such changes were being made to the Indian law. As soon as the law changed, Novartis filed a patent application for the beta crystalline form of imatinib mesilate (GLIVEC) in 1998. Imatinib as a free base molecule was invented by Novartis in 1992 and patented in the US and other countries in 1993. Novartis however chose not to apply for a patent for the imatinib free base in India then [It is pertinent to note that the 1993 US patent of imatinib disclosed the salt imatinib mesilate]. When it applied for the beta crystalline form of imatinib mesilate in 1998, the Chennai Patent Office ruled that it is a new form of a known substance and therefore not patentable under Section 3(d) of the Indian Patent Act which states that patents will not be granted for "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." Knowing fully well about this requirement of the Indian law, Novartis tried to demonstrate that there was indeed enhancement of efficacy and submitted data indicating enhanced bioavailability of 30% in studies conducted on rats. Bioavailability is one of the key parameters that decide how much of a drug would be available at its site of action in the body but there is no clear-cut or universally applicable criteria to judge to what extent alteration of bioavailability affects the efficacy of a drug. Further, results from animal studies cannot be directly extrapolated to human beings. Novartis did not demonstrate how 30% increase in bioavailability in rats could make a difference to efficacy in humans when compared to known efficacy. Therefore, the Patent Controller rejected this submission and held that Novartis had failed to demonstrate the enhancement in efficacy as required under the Act

Subsequent turn of events and portends for the future
On 17 May 2006, Novartis filed two sets of cases in the Chennai High Court – the first challenged the order of the Chennai Patent Office, which had rejected the GLIVEC patent application, following a pre-grant opposition by the Cancer Patients Aid Association. The second challenged the constitutionality of Section 3(d) of the 2005 Indian Patent Act that was specifically introduced by the Indian parliament as a safeguard against the misuse of the product patent regime. Novartis in its petition claimed that the section is not in compliance with the TRIPS Agreement and hence should be declared unconstitutional.

Section 3(d) of the Indian Patent Law is an important public health safeguard aimed at preventing pharmaceutical companies from obtaining patents on trivial improvements or new medical uses of known molecules. The law does not consider such innovations as inventions, unless an enhancement in efficacy is proven. This does not violate the TRIPS agreement, since TRIPS does not define what an invention is and allows WTO member countries to freely determine the appropriate method of implementing the provisions (Article 1) of TRIPS. Indeed the Doha Declaration requires that the TRIPS agreement is implemented in such a manner that it allows for measures to ensure access to medicines for all. Section 3(d) is an example of such a provision, incorporated in India law.

Novartis’ petition before the court challenging the constitutional propriety of Section 3(d) of the Indian Patent Act, on the grounds that its provisions were vague and arbitrary, is actually a contradictory stand since the company had tried its best to plead its case on the lines of Section 3(d) before the Patent Controller. On August 6, 2007, the Chennai High Court dismissed the challenge to Section 3(d) of the Act, but it directed the transfer of the other batch of writ petitions, requesting quashing of the Controller’s order, as a statutory appeal to the Intellectual Property Appellate Board (IPAB), by now constituted as an appeal mechanism under the Patent Act. The court did not rule on whether 3(d) is compliant with TRIPS, declaring that this issue is within the jurisdiction of the WTO rather than the court.

Unfortunately, Novartis’ claim that its actions in India will not hinder the supply of medicines to the poor is invalid since it is obvious that the direct consequence of Novartis’ action of challenging section 3(d) of the Indian Patent Act 2005, if it were successful, would have led to removal of a key safeguard designed to deny frivolous patents and would have effectively restricted Indian companies from continuing to supply generic essential medicines at affordable cost. Indeed, the impact would stretch far beyond the realm of cancer and GLIVEC, and negatively affect accessibility and affordability of many essential medicines, including crucial antiretroviral drugs for HIV/AIDS patients.

Broader implications of the controversy and fresh challenges
The story of the breakthrough anticancer drug GLIVEC in India, centering on patent applications by the innovator Novartis during a period of radical transition for India's patent laws, is complex and forces a critical look at certain vital issues of global importance.

The recent Indian court ruling is not simply about infringing on a patent, as with compulsory licensing of antiretroviral drugs in Thailand, but rather expounds the judicial view that the pharmaceutical industry must be content to earn profits only on its initial patents on an active ingredient (the original innovation) and that the industry will not get renewed patent protection for subsequent small improvements (incremental innovation) in India unlike in the US. Incremental innovation is always a grey area since what constitutes significant improvement is always open to debate. But it is wrong to assume, as Novartis or its supporters would like us to believe, that Section 3(d) stifles innovation. What it actually does is to add the responsibility of demonstrating significant improvement of efficacy in order to qualify for renewed protection. It will not choke genuine improvements but will bar frivolous 'tweaking' which are then sought to be protected under the garb of incremental innovation. Indeed, Section 3(d) is a trendsetting provision, since such a check on frivolous patenting is not to be found in the patent legislation of any country and has been hailed as a model for the world.

Imatinib was an original invention, the Indian patent office reasoned, when Novartis patented it in the US and other countries in 1993. However, that date of discovery was two years before the 1995 date when drugs became eligible for patent protection in India. Imatinib mesilate was viewed as an incremental innovation for which Novartis was unable to substantiate significant enhancement of efficacy in its 1998. Novartis took a calculated risk of not applying for an Indian patent in 1993 and did so when the law changed to permit product patents. Having taken this route, which proved a risky one, it is not proper to denigrate Indian law because it could not achieve what it wanted. Further it is unfair to prod Indian courts to use WTO’s rules to strike down laws enacted by India's parliament.

TRIPS requires that patentable inventions be new and involve an ‘inventive step’. Novartis contends that TRIPS gives WTO members the option of providing patent rights more generous than these basic criteria would mandate but does not allow members to go in the opposite direction by implementing stricter requirements for obtaining a patent. However, TRIPS does not define an ‘inventive step’; it permits (but does not require) WTO members to equate this criterion with the ‘non-obviousness’ requirement of US patent law and thus gives member countries the flexibility to fine-tune their inventive-step criteria in consonance with their socioeconomic conditions. Section 3(d) of India's patent law does not necessarily impose stricter requirements than are used elsewhere; it suggests a general presumption of nonpatentability for modifications of known chemical compositions and shifts the burden of rebutting this presumption in each particular case to the patent applicant.

The irony is that while Novartis waged its legal battle to try to coax India towards the US stand on incremental innovation, the American view of the patent system was shifting closer to India's. Even the former president of Switzerland, Novartis' own country, who had chaired an Intellectual Property Commission for the World Health Organization (WHO), saw the drug company's moves as an attempt to prevent India and the developing world from using the flexibility on patents provided by international agreements.

The original Indian Patent Act of 1970 has had a far-reaching impact on India’s economy. Since it did not allow product patents on medicines, by producing cheaper generic versions of drugs that were patented in other countries, India became a key source of affordable essential medicines. From a country which had no worthwhile pharmaceutical industry to speak of at the time of independence, it is now the base of a world-class generics industry that is supplying medicines at affordable cost to a large number of developing as well as developed countries and has emerged as the ‘pharmacy of the world’s poor’. It is now the country with the maximum number of US FDA (this is arguably the most stringent drug regulatory authority in the world today) standards compliant manufacturing facilities outside of the US. The Indian government now supports the expanded availability of patent protection as a catalyst that may enable India's pharmaceutical industry to evolve from reverse engineering to innovation. However, if Novartis succeeds in getting its patent and further changing the Indian law to resemble patent laws in wealthy countries, that purpose would be defeated. Patents may be granted in India as extensively as they are in wealthy countries, but that would mean that fewer and possibly no generic versions of new essential medicines can be produced by Indian manufacturers during the patent terms of at least 20 years, which may even be extended further through ‘evergreening’ under the veil of incremental innovation. This will have a devastating impact on India’s domestic population as well on people around the world who rely on affordable medicines from India.

However, as of now the public health safeguard built into Indian patent law has successfully passed the test of judicial scrutiny. This means that it will be much harder for pharmaceutical companies now to gain patents for products that are based on minor changes to, or combinations of, existing drugs. At present, there are about 9,000 pharmaceutical patent applications being reviewed by Indian patent offices. Many of these may be for drugs that would qualify as essential medicines. It is less likely now that many of these drugs will be patented in the future. This may encourage generic manufacturers in India to continue developing drugs that will compete with high-priced innovator brands, thereby driving down prices. This impact may be profound on the treatment of cancer, HIV/AIDS and other diseases for years to come.

The battle for ‘patients not patents’ has been won for the time being but the challenge remains. Novartis is carrying on its patent campaign into the political arena, ignoring many voices of reason from around the world. It has threatened India by airing the opinion that its favored investment destination is China. Novartis does not have the right to appeal to WTO which can be exercised only by member countries and not individual organizations or groups. But it is a pharmaceutical manufacturer of awesome economic clout and might try to influence opinion at the WTO discreetly.

Only time can tell whether there is any truth in the assertion by Novartis that the judgment will hinder innovation in this country. The prophets of doom have signaled the end of cutting-edge pharmaceutical research activities in India. Yet, there is the disturbing fact that despite increased patent protection worldwide in the last two decades, drug innovation has actually declined. Do patent rights, as they are sought to be exercised today, facilitate or hinder innovation? Perhaps it is time for governments and thinkers to consider an alternative to the system of patents that would not only provide incentive for research and development of newer drugs and vaccines but also ensure the availability and affordability of these new medicines.

Making Novartis see reason
The self-styled protectors of the world’s innovation capability at Novartis have so far remained immune to all voices of reasons from around the world, including Heads of States and highly respected global humanitarian organizations such as Medecins sans Frontieres (MSF). Many approaches have been suggested and are being undertaken.

The boycott Novartis campaign has seen a degree of success. Yet indefinite boycott is probably not desirable since Novartis does manufacture essential medicines other than GLIVEC and many patients, in the developed and developing world, having been using these medicines to their benefit. Short-term intense boycott campaigns, however, can be useful by virtue of their dramatic nature.

Medical practitioners serve as the essential link between people and drug companies as the latter depend on doctors for sale of their products. Sensitizing medical practitioners to the issue and requesting their support in the campaign by selectively boycotting Novartis products (say 2 products per doctor) can possibly sensitize Novartis. This may not only help with respect to GLIVEC but will send shock signals to other pharmaceutical companies who would otherwise indulge in similar acts.

The final and most important, albeit also the most difficult, approach would be sensitize civil society at large to the issues in question, moving from cancer and GLIVEC to the issue of the fundamental right to healthcare and access to essential medicines. Creating public awareness, on a difficult issue such as this, has no short-cuts and results cannot be expected overnight. Yet, if there is one thing which any profit making enterprise is afraid of, it is adverse publicity that destroys its image. This is the only cry of shame that Novartis is likely to listen to and the job before access to essential medicine campaigners now is to kindle this collective cry of shame to force Novartis to abandon its unbridled ‘profits before patients’ mentality.


References
1. Protein kinase inhibitors. British National Formulary 2007; (53): 459-60.
2. Mueller JM. Taking TRIPS to India - Novartis, patent law, and access to medicines. The New England Journal of Medicines 2007; 356(6): 541-3.
3. Dabade G, Upadhyay R. Falling sick is no sin. Deccan Herald. August 12, 2007 (Accessed January 18, 2008 at http://www.deccanherald.com/Content/Aug122007/panorama2007081118582.asp)
4. Menghaney L. Indian law is a model. Deccan Herald. August 12, 2007 (Accessed January 18, 2008 at http://www.deccanherald.com/Content/Aug122007/panorama2007081118584.asp)
5. Bringardner J. Novartis' India missteps leave patent questions. Law.com. October 3, 2007 (Accessed January 18, 2007 at http://www.law.com/jsp/law/LawArticleFriendly.jsp?id=1191229387137)
6. Novartis loses Indian patent law case. Chemistry World news. August 6, 2007 (Accessed January 18, 2008 at http://www.rsc.org/chemistryworld/News/2007/August/06080703.asp)


Acknowledgement
Dr. Avijit Hazra. Reader – Department of Pharmacology, IPGME&R, Kolkata.

Sunday, September 2, 2007

BOYCOTT NOVARTIS


  1. Introduction,

  2. Patents vs. Profits; - A VICTORY,

  3. Novartis – the company – The story of Novartis,

  4. Mashelkar, NCE & Novartis,

  5. E-drug, INDIGENT – Drug donation programme,

  6. E-drug responses, Doctors & Brands

  7. List of drugs manufactured by Novartis

  8. Boycott Letter to Novartis,

Wednesday, August 15, 2007

DAF-K relaunches BOYCOTT NOVARTIS CAMPAIGN

Tuesday, August 14, 2007

Dear friends,

Drug Action Forum - Karnataka in its meeting on Saturday, 11th August 2007 decided to relaunch NOVARTIS BOYCOTT CAMPAIGN, with vigour than ever before.

This stand had to be taken in view of a situation that has been precipitated by Novartis. On 6th August 2007, when the judgment in Chennai high court was made, DAF-K members rejoiced and were feeling that the issue is more or less come to some conclusive end. But not so! Novartis has filed another case in Chennai high court on 8th August 2007. Few media reports have appeared and please scroll below for it.

For prescribing doctors - a list of drugs manufactured by Novartis - is given (please scroll below). This list is to help doctors to "BOYCOTT PRODUCTS OF NOVARTIS".

For consumers DAF-K has identified two products of Novartis that need to be BOYCOTTED. One is "Voveran" - a popular pain killer and the other is "Calcuim Sandoz".
If you are to buy a pain killer at chemist insist for Diclofenac, that is manufactured by other companies and insist to the chemist that you do NOT want to buy Voveran. Use this as an opportunity to explain the chemist as to why you are BOYCOTTING.

PLEASE JOIN THE BOYCOTT AND CONTRIBUTE.

Sunday, August 12, 2007

Novartis files fresh appeals

THE HINDU, Friday, 10th August 2007
High Court stays Novartis appeal

Special Correspondent

CHENNAI: All further proceedings on the statutory appeals filed by Novartis, challenging the rejection of its patent application, pending before the Intellectual Property Appellate Board (IPAB) were stayed by the Madras High Court on Thursday.

The First Bench comprising Chief Justice A.P. Shah and Justice P. Jyothimani granted the interim relief on a writ petition filed by Novartis AG stating that the IPAB had erred in dismissing its plea to exclude its Technical Member S. Chandrasekaran from hearing its statutory appeals.

The Bench has posted the matter to September 10 for further proceedings. Novartis’ application to patent the beta crystalline form of imatinib mesylate was rejected by Chennai Patent Office in January 25, 2006. In April 2007, the High Court transferred the statutory appeals to the IPAB after a Technical Member was appointed and the Board became functional.

When the IPAB took up the appeal for hearing, Novartis sought to exclude Mr. Chandrasekaran from the Bench, on the ground that he had filed a counter-affidavit in support of the Union of India and the Controller-General of Patents and Designs and hence he would be biased against Novartis. In July 2007, the IPAB rejected the objections. The present writ petition challenges the rejection of its objections.

Describing the timing of appointment of Mr. Chandrasekaran as significant, the company said the IPAB had erred in rejecting its plea to request the Centre to appoint another member in lieu of Mr. Chandrasekaran.

The January 25, 2006 order rejecting Novartis’ patent application was passed by the Assistant Controller under the aegis of the erstwhile Controller-General Chandrasekaran, the petitioner said, adding that he had deposed an affidavit against Novartis in High Court before becoming a Technical Member of the IPAB. It said he would “suffer from a prejudiced mindset and would not be able to apply his mind in an independent fashion.” It said, “It is well nigh impossible to expect that a person with an indelible mindset will be able to serve as an unbiased Technical Member (Patent).”It sought to quash the IPAB order and consequently direct the Board to remove Mr. Chandrasekaran from acting as a Technical Member (Patent) to hear the appeal and direct the Centre to appoint another Technical Member in his place.

© Copyright 2000 - 2006 The Hindu

Monday, July 23, 2007

http://www.deccanherald.com/Content/Jun182007/editpage200706178009.asp
Deccan Herald, Edit Page, Detailed Story, Monday, 18th June 2007IN PERSPECTIVE,
Patents for Profits
By Gopal Dabade

If Novartis wins, other MNCs would also claim patents for well-known medicines.

A case filed by a big drug company has attracted global attention. "Doctors Without Borders" – winner of the Nobel Prize for best medical relief in 1999, has requested people all over the world to write to the company to drop the case. Over two lakh people have written to Novartis. Why is this case so important?

Novartis, the Swiss Multinational pharmaceutical company, has filed a case in the Chennai High Court against the order of the Chennai Patent office rejecting the patent application filed by them for getting a patent on imatinib mesylate, a medicine useful in the treatment of chronic myeloid leukemia (CML) - a form of blood cancer. Currently it is being produced in its generic form by NATCO, Cipla, Ranbaxy and Hetero as well as by Novartis under the brand name Gleevec. Treatment with Gleevec, the Novartis brand costs Rs 1.2 lakh per month, whereas the Indian generic versions cost about Rs 8000 ($175)! If product patent is granted to Novartis, the Indian generic versions will be forced to go out of the market, while the treatment of the CML would cost Rupees 1.2 lakh per month and this would go out of the reach of 99 per cent of the patients of CML. There is no explanation as to why Novartis is not offering different prices depending on the circumstances in a country like India.

ObjectionableThe Novartis' claim for patent on the beta crystalline form of imatinib mesylate is objectionable because though this beta crystalline form is less hygroscopic, is easier to process, stores better -- it doesn't satisfy the two essential criteria of patentability as specified by section 3(d) on the amended Indian Patent act – innovative step and non-obviousness to those familiar with the art. Imatinib mesylate is not a new molecule. Converting the already existing drug into crystalline form is not an innovative step nor is not non-obvious. To claim a patent on the crystalline salt form of imatinib mesylate is entirely unacceptable. Hence in January last year, the Chennai Patent office rightly rejected the Gleevec patent application on the ground that the application claimed "only a new form of an old drug".

Novartis claims that those patients, who cannot afford to purchase Gleevec, receive the drug free of charge, through Novartis' Glivec International Patient Assistance Programme (GIPAP). Novartis says that 6,700 patients get free Gleevec, whereas in India 20,000 patients suffer from chronic myeloid leukemia every year. Dr Purvish Parikh, professor and chief of medical oncology, Tata Memorial Hospital, has filed an affidavit based on his experience, debunking the claim of the company about GIPAP.

ConstitutionalityThe second case filed by Novartis challenges the constitutionality of section 3(d) of the Indian Patents Act, specifically introduced by the Indian parliament as a safeguard against the misuse of the product patent regime. Novartis is claiming that the section is not in compliance with the TRIPS agreement. Each country can introduce a patent regime that is more suited to its socio-economic context. This is also in keeping with the 2001 Doha Declaration on the TRIPS Agreement and public health. Secondly, looking at the issue from a legal angle, section 3(d) can be challenged by a government and not by a company.

Novartis claims that the Chennai Patent Office's rejection of Novartis patent for Gleevec violates TRIPS. If so then this claim should be taken to the special international dispute redressal mechanism under WTO, which deals with such matters. However, instead, Novartis has decided to approach the Chennai High Court.

If Novartis wins this case, other MNCs would also claim patents for similar, already well-known medicines and there will be the danger of making a series of medicines out of the reach of ordinary Indians. Since India also supplies cheaper, generic drugs to the tune of thousands of crores to many developing countries, this will also be adversely affected. Hence thousands of people all over the world have signed an online "drop the case" letter to Novartis. The campaign has been launched by "Doctors Without Borders" (http://www.doctorswithoutborders.org/).

Thursday, July 12, 2007

Boycott Novartis

DRUG ACTION FORUM – KARNATAKA,
57, Tejaswinagar, Dharwad 580002, Karnataka, India.

1st July 2007

Dear friends,

Greetings,

Drug Action Forum – Karnataka (DAF-K) is an independent, voluntary and registered non government organisation campaigning for Rational Drugs. DAF – K is part of Jan Swastya Abhiyan (JSA is People’s Health Movement – India, http;//phm-india.org). DAF –K is also member of AIDAN (All India Drug Action Network, http://www.aidanindia.org/) and HAIAP (Health Action International Asia Pacific http://www.haiap.org/).

We are writing to you on a matter that can deeply affect access to medicines for your patients. The issues we highlight in this appeal are two-fold – one pertaining specifically to access to treatment for thousands of patients suffering from Chronic Myeloid Leukaemia (CML) and the other to a broader issue of the cost of new medicines that may be provided Patent protection. We would urge you to read this appeal carefully and consider taking the measures suggested in it.


Background

As you might be aware, Novartis, a Swiss multinational drug company operating in India, has been involved in challenging the laws of our country through two petitions filed in the Chennai High Court. The facts of the two cases that Novartis has filed against the Indian Government are explained below.


In the first case, Novartis has challenged the order of the Indian Patent office in Chennai, rejecting its application for a patent on imatinib mesylate, which Novartis markets in India under the trade name: Gleevec. As you would know, imatinib mesylate is extremely useful in the treatment of chronic myeloid leukemia (CML). In addition to Novartis, several Indian companies – viz. NATCO, Cipla, Ranbaxy and Hetero -- also produce and market the drug. Treatment with Gleevec (manufactured and marketed by Novartis) costs Rs 1.2 lakh per month, whereas the same drug is marketed by Indian companies at a cost of about Rs. 8,000 per month. If a patent were to be granted to Novartis for imatinib mesylate, Indian companies would be forced to stop production of the drug. As the treatment cost would be of Rs.1.2 lakh per month, this would mean that over 99% of patients requiring the drug would be denied access to it. The huge difference in the price of the same drug is an illustration of how a patent monopoly can be used by drug companies to generate super-profits while endangering the lives of thousands, or even millions.


Rejection of Novartis’ Patent Application by Patent Office

The Indian Patent office had rejected the application for a patent on sound principles, entirely consistent with the country’s laws and the agreement on Trade Related Intellectual Property Rights (TRIPS), to which India is a signatory. Novartis had obtained a patent for the same drug in 1993, i.e. two years before the TRIPS agreement was signed. At that time the Indian law did not recognise patents on pharmaceutical products. As per the TRIPS agreement, if a drug has been patented before 1995, countries like India which did not recognise patents on medicines before the signing of the TRIPS agreement do not have to recognise such patents. Novartis tried to circumvent this by filing a fresh patent application in India for the beta crystalline form of the same drug. Novartis claimed that this form of the drug was an advance on its earlier patent on the “amorphous” form, because it is less hygroscopic and hence more stable. The patent office rejected this application because it felt that the application was not for a “new” molecule and someone who understands the chemistry of the patented molecule (imatinib mesylate) would realise that the beta crystalline form of the molecule would have these useful properties. Thus it opined that the patent application failed on two counts for the required criteria of patentability – it did not demonstrate an “innovative step” and it was not a “non-obvious” invention. The Patent office further felt that the application by Novartis was not consistent with section 3(d) of the Indian Patent Act, which specifically states that a different structural form of a known substance cannot be patented. Hence in January 2006, the Patent office rejected the Gleevec patent application on the ground that the application claimed ‘only a new form of an old drug’.

Novartis claims that those patients, who cannot afford to purchase Gleevec will receive the drug free of charge, through Novartis’s Gleevec International Patient Assistance Programme (GIPAP). What it does not say is that this programme was started in India because, before Novartis’ patent was rejected and it had an exclusive marketing right on the drug and the Chennai High Court had specifically asked that Novartis provide access of this drug to all those who need it and whose monthly income was less than Rupees 3,50,000. Further, while Novartis claims that 6,700 patients get free Gleevec, there are an estimated 20,000 new of chronic myeloid leukemia every year.

Novartis Challenges our Country’s Law

Novartis has filed a second case – one which challenges the constitutional validity of Section 3(d) of the Indian Patents Act. It may be recalled that Section 3(d) was specifically introduced by the Indian parliament as a safeguard against the misuse of product patents on medicines. Novartis has claimed that this section is not in compliance with the TRIPS agreement and is in violation of the Indian constitution. Many experts have confirmed that Section 3(d) conforms to the requirements of the TRIPS agreement, as the agreement clearly allows each country to set its criteria of patentability and does not prevent countries from including safeguards against the grant of fresh patents on old drugs. Section 3(d) is also in keeping with the “Doha Declaration on the TRIPS Agreement and Public Health” that was adopted by the Ministerial meeting of the WTO, held in Doha in 2001.

This challenge by Novartis is of particular concern for several reasons. It is a matter of grave concern that a foreign company has chosen to challenge the constitutionality of a law that has been passed by the Indian Parliament to safeguard public health. Members of the medical profession need to be particularly concerned about such cynical use of India’s legal system. The company has legally circumvented this issue by filing the case through its Indian subsidiary, but the fact remains that the challenge has been made on the directions of a foreign entity. Further, the company’s contention that Section 3(d) of India’s Patent Act violates the TRIPS agreement cannot be heard by Indian courts as they do not hear appeals regarding conformity of Indian law to international treaties. Such a challenge needs to be made in the World Trade Organisation’s Dispute Settlement Mechanism, and that too can be made only by a member state of the WTO and not by a private corporation. No government has, till date, challenged the Indian law in the WTO. Interestingly, the company’s arguments regarding the constitutional validity of the Indian law have been shifting continuously, even while the case was being heard. Initially it had not made out a case on the issue of constitutionality, but later changed its line of attack to argue that the language used in section 3 (d) was vague and not used anywhere in the world and that it did not give enough guidelines to the Patent Controller.

It should be understood that if Section 3(d) of the Indian Patents Act was to be removed it would open the door for a large number of trivial patents. This Section 3(d) is the principal safeguard against the misuse of the Patent system by the patenting of known medicines, by making slight modifications in their structure. Such patents do not contribute to any therapeutic benefits but do contribute to increase corporate profits by extending patent monopolies on frivolous grounds. Thus the removal of this important section would mean many new medicines would have to be granted patents on trivial grounds and multinational corporations like Novartis, who hold these patents, would charge exorbitant amounts for these medicines.

Clearly, the challenges posed by Novartis to the Indian law constitute an attempt to profiteer at the expense of tens of thousands of poor and sick patients. It is also an attempt to open the floodgates for other drug companies so that they too can apply for trivial patents. The consequences will not be just limited just to India. Today India is known globally as the “Pharmacy of the Third World”, because Indian companies export cheaper versions of patented drugs to over 150 countries. For example, over half the medicines currently used for AIDS treatment in developing countries come from India. If Indian companies are to be prevented from making generic versions of patented drugs, tens of thousands of poor patients in Africa, Asia and Latin America will be denied access to essential medicines. That is why hundreds of thousands of people all over the world have signed an online ‘drop the case’ letter to Novartis, asking it withdraw the case it has filed in the Chennai High Court. The ‘Drop the Case’ campaign has been launched by the organisation, “Doctors Without Borders” (http://www.doctorswithoutborders.org/) – winner of the Nobel Prize Award for best medical relief during the year 1999. Many reputed personalities have publicly appealed to Novartis to withdraw the court case. They include Erik Solheim, Minister of International Development, Norway and Henry Waxman, Chairman, Congress of United States. Separately, our Health Minister, Dr.Ambumani Ramados has also appealed to Novartis to drop the legal challenges. In spite of such appeals, however, Novartis continues to pursue the court cases vigorously.


Appeal to you as a Medical Professional

It is in this background that, on behalf of Drug Action Forum - Karnataka, we are sending this appeal to you to do the following:

1. Boycott products that are manufactured and marketed by Novartis in India by refraining from prescribing drugs that are marketed by Novartis. We feel that your action will be a powerful message to the Swiss Company. Medical professionals are an important link between the people and the pharmaceutical industry as the latter depend on for the sale of their products. Drug Action Forum - Karnataka sincerely feels that your action can be decisive. The campaign for boycott is proposed to last till Novartis stops its actions that prevent patients from getting access to essential medicines. This includes dropping all legal actions related to imatinib mesylate (Gleevec) including the upcoming appeal to the patent controller’s order and stopping their actions in trying to influence the Indian government to introduce laws and policies that create monopolies on drugs and that place profits before patients. The Drug Action Forum - Karnataka is compelled to call for this boycott as a last resort, and in this we seek your support because Novartis has failed to respond to all other approaches by leading global organisations and state heads. As a professional who places the welfare of her or his patients foremost, we believe that you will agree to join this Campaign. This is a campaign that is not just about one medicine, but also about the broader issue of ensuring access to essential medicines and of holding pharmaceutical companies accountable to their societal duties.

For your ready reference we are providing a list of drugs marketed by the company Please scroll below). We are sure that you will find therapeutically equivalent or superior substitutes for virtually all these medicines from those marketed by other companies in the country. In case however you feel the need to continue prescribing a drug marketed by Novartis because of the absence of a suitable substitute, we would still urge you to sign the petition below.

2. We also appeal to you to sign the letter (please scroll below for the letter) that urges Novartis to desist from jeopardizing the lives of countless poor and sick people and send it to the Drug Action Forum - Karnataka at the address mentioned.

Do feel free to edit the suggested contents of the letter to reflect your personal understanding of the issue. It would be useful if the letter were composed on your personal pad. Please do not hesitate to contact us for more details through email or cell phone or correspondence.

Sincerely,
(Dr Gopal Dabade),
President, DAF-K,
Cell 09448862270
(Mr Khan A M)
Secretary, DAF-K,
Cell 09448378593
(Dr S L Pawar)
Jt; Secretary, DAF-K,
Cell 09449354415


List of medicines manufactured / marketed by Novartis in India

  1. 3-FD (Anti-TB combination, INH + Rifampicin + Pyrazinamide),
  2. 4-D (Anti-TB combination, INH + Rifampicin + Pyrazinamide + Ethambutol)

  3. Adelphane (Drug for high blood pressure; Reserpine + Dihydrallazine)

  4. Adelphane / Esidrex (Drug for high blood pressure; Reserpine + Dihydrallazine + Hydrocholothiazide)

  5. Anafranil (Antidepressant; Clomipramine)

  6. Angicor (Prophylaxis of angina and post myocardial infarction; Isosorbide-5-Mononitrate)

  7. Antrenyl and Antrenyl Duplex (Drug for peptic ulcer and colicky pain; Oxyphenonium Br)

  8. Aredia (Drug for bone disorders and high calcium levels; Pamidronate)

  9. Aubril (Antimicrobial; Sulfadiazine + Trimethoprim)

  10. Benace (Drug for high blood pressure; Benazepril)

  11. Bradex-Vioform (Anti-infective skin cream; Quinodochlor + Tripelennamine + Domiphen Br.)

  12. Brinaldix (Oedema due to CCF, renal or hepatic failure; Clopamide)

  13. Broadband (Antimicrobial; Gatifloxacin)

  14. Calcium–Sandoz (For treating calcium deficiency; Cal glubionate)

  15. Clearance (Eye drops; Naphazoline)

  16. Cletus (Platelet aggregation inhibitor and vasodilator; Cilostazol)

  17. Curam (Antimicrobial; Amoxicillin and Clavilonic acid)

  18. Daskil (Antimicrobial; Terbinafine)

  19. Desferal (Acute iron poisoning; Desferrioxamine)

  20. Dibimet (Hypoglyceamic agent; Metformin in with combination with starch and cellulose and others)

  21. Diovan (Following M I in clinically stable patients with left ventricular failure; Valsartan)

  22. Ebutol (Anti TB; Ethambutol)

  23. Epitril (Benzodiazepine for treating seizers etc; Clonazepam)

  24. Exelon (Sysmptomatic treatment of severe Alzheimer’s dementia; Rivastigmine)

  25. Foristal (Allergic conditions; Dimethindene maleate), Foristal lontabs

  26. Genteal (Eye lubricant; Boric acid, Hydroxyl propyl, KCL, NaCl, Methyl cellulose and Sod perborate)

  27. Glyred M (Hypoglyceamic agent; Metformin, Gliclazide, cellulose, starch and others).

  28. Hematrine (To treat anaemias; Ferrous suc, Succinic acid, Folic acid, Vit C, B-12, Nicotinamide)

  29. Hydergine (Ergot alkaloid for primary dementia; Dihydroergotoxine)

  30. Hypotears plus (Eye lubricant; Boric acid, CaCl2, MgCl)

  31. Leucomax (Acceleration of myeloid recovery following bone marrow transplant; Molgramostim GM-CSF).

  32. Liquidix SR (Mucolytic therapy in diseases of lungs; Ambroxol)

  33. Lioresal (Spastic conditions of skeletal muscles; Baclofen)

  34. Lopresor (Beta blocker; Metoprolol)

  35. Lodiric (Anti-hyperuricaemic agent; Allopurinal)

  36. Loromycin (Antimicrobial; Azithromycin)

  37. Macalvit (Increased calcium demand like pregnancy; Cal glucono-galacto-gluconate, Cal lactbionate, Vit B-12, D-3)

  38. Methergin (Post partum and post abortal bleeding; Methylergometrine maleate)

  39. Miacalcic (Established post menopausal osteoporosis; Salmon calcitonin)

  40. Miacalcic (Established postmenopausal osteoporosis; Salmon calcitonin)

  41. Millicortenol (Eczema, dermatitis etc; Dexamethasone) Millicorten-Vioform (Anti bacterial and antimyocotic topical; Dexamethasone, Quiniodchl).

  42. Nepresol (Anti-hypertension; Dihydrallazine sulphate)

  43. Nitroderm TTS (Prevention of angina pectoris; nitroglycerine in transdermal patch)

  44. Nutrisan (Vitamin/mineral deficiency; Vit A, Vit D, B-1, B-2, Nicotinamide, B-6, Folic acid, C, Vit B-12, Ferrous fum, Mang chl, Mag oxide, Cal gluconate, Zinc oxide).

  45. Nyolol (For treating glaucoma; Timolol)

  46. Okacin (Eye preparation; Lomefloxacin)

  47. Otrivin (Nasal decongestion; Xylometazoline)

  48. PZA-Ciba (Anti-TB; Pyrazinamide)

  49. Parlodel (For treating Parkinsonism, Galactorrhoea and others; Bromocriptine)

  50. Regestrone (Synthetic progesterone; Norethisterone acetate)

  51. Resource (Food product)

  52. Rimactane (Anti-TB; Rifampicin)

  53. Rimactazid-Z (Anti-TB combination; Rifampicin, Isoniazid, Pyrazinamide)

  54. Rimastar 4FDC (Anti-TB combination; Ethambutal, INH, Pyrazinamide, Rifampicin)

  55. Rimicure 3FDC (Anti-TB combination; Ethambutal, INH, Pyrazinamide, Rifampicin)

  56. Rimmax 2FDC (Anti-TB combination; INH, Rifampicin)

  57. Rimthree FDC (Anti-TB; Ethambutol, INH, Rifampicin)

  58. Rotacor (Anti-hypercholesterlaemia; Atorvastatin)

  59. Sandimmun Neoral (Prevention of graft rejections; Cyclosporine)

  60. Sandocal (For treating vitamin D deficiency; Vit D3, Cal carbonate)

  61. Sandostatin (Relief of symptoms associated with gastroenteric-pancreatic endocrine tumors; Octreotide)

  62. Santevini (Tonic; Thiamine mononit, Vit B-2, B-6, Niacinamide, Peptone, Cal gluconate)

  63. Secef (Antimicrobial; Cefixime)

  64. Sclerace (Antihypertensive; Rampril)

  65. Sirdalud (Spasticity, trauma, cerebral palsy and others; Tizanidine)

  66. Sintamil (Tricyclic antidepressant; Nitroxazepine)

  67. Spert (Protein supplement with vitamins and minerals)

  68. Sulcef (Antimicrobial; Cefoperazone; Sulbactan)

  69. Syntocinon (PPH and acceleration of labour; Oxytocin)

  70. Taregyl tablets (Antihistamine; Clemastine)

  71. Tavegyl syrup (Antihistamine; Clemastine)

  72. Tegritol (For Trigeminal neuralgia; Carbamazepine)

  73. Trioptal (Anti-epileptic; Oxcarbazepine)

  74. Urclar (Antimicrobial; Clarithromycin)

  75. Visken (For angina; Pindolol)

  76. Voltaflam (Antinflammatory ;Diclofenac)

  77. Voveran (Antinflammatory; Diclofenac)

  78. Zetri (Antimicrobial; Ceftriaxone)

  79. Zometa (For tumor induced hypercalcaemia; Zoledronic)

From;-
DRUG ACTION FORUM – KARNATAKA,
57, Tejaswinagar, Dharwad 580 002. INDIA
Email drugactionforumkarnataka@gmail.com
Cell 9448862270
Phone 0836 2461722
http://www.daf-k.cjb.net/
COPY OF LETTER DRAFT TO NOVARTIS
Date

To,
Novartis India Ltd,
Sandoz House,
8th floor,Shivsagar Estate,
Dr Annie Besant Road,Worli,
Mumbai 400 018, India.
Fax 022 24950221

Sir,
Over the past year, media and other reports have highlighted Novartis’ actions in India and abroad in impeding the access of patients to essential medicines. The highlight of Novartis’ actions in India has been your company’s challenge to the decision of Chennai patent office that rejected your claim for imatinib mesylate by filing a case in Chennai High Court. In doing so you have taken the Indian government and cancer patients to court over absolutely essential public health protections in India’s patent law. It is unfortunate that you have taken such a decision and it is your decision to not drop the case in spite of pressure from Indian and global quarters and to actively promote policies that prevent people from accessing medicines that has sparked the doctors’ community to take the ultimate decision of “BOYCOTTING OF ALL PRODUCTS OF NOVARTIS”.
Your company’s claim for patent on the beta crystalline form of imanitib mesylate is objectionable under India’s patent law. Even after your patent application was rejected, you continue to pursue your attempt to get a monopoly on this drug. In doing so, Novartis has done the unthinkable and challenged the constitutional validity of an important public health safeguard in Indian law which ensures access to essential medicines. Hundreds and millions of people all over the world depend on drugs produced by Indian generic companies and Novartis’ case may have an impact on this.
Your company’s version of imatinib mesylate is sold in the market for Rupees 1.2 lakhs per patient per month; where as the same drug is sold by Indian generic companies for Rupees 8,000. Such enormous expenses for the drug will make the drug beyond the reach many of Indians. Novartis has never been able to explain why it has chosen to market this drug at such an exorbitant global price; why it does not take into account the different circumstances in different countries and offer different prices.
Further your company’s claims that those patients, who cannot afford to purchase your version of imatinib mesylate, receive the drug free of charge, through your own company’s outlet by name ‘Glivec International Patient Assistance Programme’ (GIPAP). But it is well known that only 6,700 patients get the drug from you free, whereas in India 20,000 patients suffer from chronic myeloid leukemia every year. Moreover, it is the right of every patient to get life saving medicines; we strongly object to any system that puts our patients at the mercy of the charity of a company.
Given the realities mentioned above it is strongly urged that your company should drop all legal proceedings in India in the imatinib mesylate case including the upcoming appeal to the patent controller’s order. And we the Doctors Community will continue the boycott of all your products till you stop your legal actions; till you drop your global price for imatinib mesylate; till you stop trying to influence the Indian Government to introduce laws and policies that hinder access to medicines; in particular till you stop your actions in trying to push for further monopolies like data exclusivity.
The greatest duty of the medical doctor is to save the lives of people and we are doing it now by boycotting your company’s products as the doctors’ community is left with no other choice because of your stand.

Yours truly,

From:-


Copy to;- DAF-K, 57, Tejaswinagar, Dharwad 580 002.

Wednesday, July 11, 2007

Date
To,
Novartis India Ltd,Sandoz House, 8th floor,Shivsagar Estate,Dr Annie Besant Road,Worli, Mumbai 400 018, India.Fax 022 24950221

Sir,
Over the past year, media and other reports have highlighted Novartis’ actions in India and abroad in impeding the access of patients to essential medicines. The highlight of Novartis’ actions in India has been your company’s challenge to the decision of Chennai patent office that rejected your claim for imatinib mesylate by filing a case in Chennai High Court. In doing so you have taken the Indian government and cancer patients to court over absolutely essential public health protections in India’s patent law. It is unfortunate that you have taken such a decision and it is your decision to not drop the case in spite of pressure from Indian and global quarters and to actively promote policies that prevent people from accessing medicines that has sparked the doctors’ community to take the ultimate decision of “BOYCOTTING OF ALL PRODUCTS OF NOVARTIS”.
Your company’s claim for patent on the beta crystalline form of imanitib mesylate is objectionable under India’s patent law. Even after your patent application was rejected, you continue to pursue your attempt to get a monopoly on this drug. In doing so, Novartis has done the unthinkable and challenged the constitutional validity of an important public health safeguard in Indian law which ensures access to essential medicines. Hundreds and millions of people all over the world depend on drugs produced by Indian generic companies and Novartis’ case may have an impact on this.
Your company’s version of imatinib mesylate is sold in the market for Rupees 1.2 lakhs per patient per month; where as the same drug is sold by Indian generic companies for Rupees 8,000. Such enormous expenses for the drug will make the drug beyond the reach many of Indians. Novartis has never been able to explain why it has chosen to market this drug at such an exorbitant global price; why it does not take into account the different circumstances in different countries and offer different prices.
Further your company’s claims that those patients, who cannot afford to purchase your version of imatinib mesylate, receive the drug free of charge, through your own company’s outlet by name ‘Glivec International Patient Assistance Programme’ (GIPAP). But it is well known that only 6,700 patients get the drug from you free, whereas in India 20,000 patients suffer from chronic myeloid leukemia every year. Moreover, it is the right of every patient to get life saving medicines; we strongly object to any system that puts our patients at the mercy of the charity of a company.
Given the realities mentioned above it is strongly urged that your company should drop all legal proceedings in India in the imatinib mesylate case including the upcoming appeal to the patent controller’s order. And we the Doctors Community will continue the boycott of all your products till you stop your legal actions; till you drop your global price for imatinib mesylate; till you stop trying to influence the Indian Government to introduce laws and policies that hinder access to medicines; in particular till you stop your actions in trying to push for further monopolies like data exclusivity.
The greatest duty of the medical doctor is to save the lives of people and we are doing it now by boycotting your company’s products as the doctors’ community is left with no other choice because of your stand.

Yours truly,
From:-

Copy to;- DAF-K & AIDAN, 57, Tejaswinagar, Dharwad 580 002.