Patent: The Daylight Dacoity Of Evergreening!

So much is made of Intellectual Property Rights that a day won’t be too far when Life itself will be patented. Reproduction or Replication, which is the life force of evolution, would then be imprisoned in the patents office. If this sounds like some Sci-Fi horror, then that is how exactly the sufferers of Chronic Myeloid Leukaemia [CML] -a particularly virulent type of blood cancer- must feel. In a country where the planning commission chief declares that those who have INR 33/day to spend on their daily needs are not living in poverty, those who can spend INR 400/-day required for the treatment of CML through even generic versions of patented drug Glivec or Gleevec would certainly look super rich.

Companies like Cipla, who are selling generic versions, are not in charity and earn enviable returns on their drug marketing activities. Novartis -the Swiss multinational- wanted much more for its patented drug, INR 4,000/day to be precise or some 10 times more. This is simply daylight dacoity whichever way one looks at it.
Mercifully, India’s apex court upheld the ruling of Intellectual Property Rights Board, who had refused to allow a patent on Glivec on the ground that it was only an amended version of the known compound Imatinib Mesylate. Novartis had argued that the beta-crystalline form of Imatinib Mesylate, which it now incorporates in its earlier patented drug, is a completely new ingredient developed in its research labs and needs continued patent protection to protect its sizable research costs. The bench held ^^^that for grant of patent, a subject must satisfy the twin tests of “invention” and “patentability“. It termed as “unacceptable” the contention that a test of enhanced efficacy was not required when the product was prima facie established to be an invention. It also referred to Novartis’s patent application, in which the company makes a “clear and unambiguous” admission that all therapeutic qualities of the beta crystalline form of Imatinib Mesylate are also possessed by Imatinib in free base form^^^. In substance, Novartis admits that beta crystalline form serves no better than free base form of the active ingredient, and moreover, former doesn’t impart enhanced efficacy. Then why did Novartis make this *innovation* at all? When patents expire, the lucrative cash cow all but dries up due to competition from cheap [?] generic alternatives. Companies seek to extend the protection of patents to this daylight dacoity by making some cosmetic changes in their formulations and then claiming them as revolutionary breakthroughs. This is a well worn tactic and goes under the rubric -evergreening.
Predictably, Novartis was unhappy by the turn of events: ^^^The verdict “discourages innovative drug discovery essential to advancing medical science for patients,” the firm said after the SC judgement. “We strongly believe that original innovation should be recognised in patents to encourage investment in medical innovation especially for unmet medical needs,” Ranjit Shahani, vice chairman and MD, Novartis India Ltd said on Monday in Mumbai… India’s failure to grant patents for critical medicines — and Glivec is widely recognised as one of the most important medical discoveries in decades — is a short-sighted strategy that undermines a vital system for funding new discoveries^^^. This is rather disingenuous twisting of facts. What the judgement does in fact is to discourage the efforts to pass on spurious innovation or rather modification as genuine drug discovery. It also discourages the practice that seeks enhanced patent protection through foregoing means beyond the period lawfully granted.  
The drug, Imatinib Mesylate, was patented in 1990s by Jürg Zimmermann. The clinical trials were started by Dr Brian Druker in 1999. ^^^Chronic myeloid leukaemia was long considered to be one of the most lethal forms of cancer. In the 1960s researchers discovered that almost all sufferers had a defective chromosome that has subsequently come to be known as the Philadelphia chromosome. This is the root cause of a certain protein that creates an abnormal proportion of white blood corpuscles^^^. Imatinib Mesylate inhibited the protein that gave rise to abnormally high WBCs. When it was introduced in the market, it showed its efficacy with minimal side effects making it a great hit in the treatment of CML. However, it is very rare that single pharma company, however big, singly produces any drug innovation. More often than not every such innovation rests on the contribution of many, who do not work for that company or for that matter any company. Many of these contributions arise out of public funding of research at universities and specialised institutions. Rarely these contributions are acknowledged, or rather every effort is made to hide them and if revealed belittle them.  
The comment by a reader -Vladileo- on a Bloomberg Article,  Novartis Cancer-Drug Patent Denied by India Supreme Court, caught my eye in the above context.
The sad part that most of the people ignore or do not talk about is that most of the research took decades and was not developed by the big pharma.
There were a lot of basic scientist involved in the discovery of the target of Gleevec and its function, like David Baltimore, Owen N. Witte at MIT that discovered the function of the ABL gene in the Abelson virus that produce leukemia in mice, Peter Nowell and David Hungerford at the University of Pennsylvania that discovered that in CML the chromosome 22 is shortened (chromosome Philadelphia) , Janet Rowley of the University of Chicago that found that the missing piece of chromosome 22 is in chromosome 9, Owen Witte found that in people with CML and chromsome philadelphia there is fuse protein made of  BCR and ABL.  Tony Hunter discovered that tyrosin can be phosphorylated. Witte found that BCR-ABL work phosphorylating tyrosin of other proteins.  Witte convince several researchers that blocking the BCR-ABL funcion with molecules could combat the disease. One of them was Brian J. Druker from the Oregon Health Sciences University, who developed a tool to test when a tyrosin is phosphorylated.  This tool was use by the company Ciba-Geigy(later Novartis) to find molecules. Because he had a close collaboration with the company, he knew that in Novartis Nicholas Lydon has developed several molecules in his effort to create and inhibitor of  epidermal growth factor receptor that  also work by phosphorylating tyrosines. The company was not interested initially in BCR-ABL but he convince them and obtain a group of those compounds for testing against the BCR-ABL in his lab. He found the molecule STI571 later imatinib (gleevec) was effective and specific  at binding  BCR-ABL and preventing its function of phosphorylation of tyrosines in other proteins. Later the first clinical trials were done with Charles L Sawyers at the Memorial Sloan-Kettering Cancer Center. Further trials were made by John Goldman from the Imperial College School of Medicine of London and Carlo Gamborcorti-Passerini from the Italian National Cancer Institute. Is important to note that according to Brian Druker, Novartis was  in the middle of a fusion the scientis Nicholas Lydon was not more working with them and the new executives were very skeptical of their work. The real support for the development of the drub began when the first clinical trials started to shows it benefits.
Scientist like Witte or Brian Druker never made any money from the sales of the drug. Their work was supported by public funding. They got papers, public recognition, honors and prizes.
 Moreover early clinical trials were support by public funding.  The research of  Novartis was also funded with credits from the government. The fundamental ideas and discoveries that ultimate in the production of the drug implicate decades of  work from several people in which Novartis has a small part but is making sure of taking all the benefits and credit.
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6 Responses to “Patent: The Daylight Dacoity Of Evergreening!”

  1. Kusum Ranganekar Says:

    "….Actually, the Court fully upheld the principle of patents, but set a high bar for deciding what's innovative and what's mere tweaking.Instead of attacking the verdict, Western countries should raise their standards too. Their overliberal grant of patents has led to the tiniest design changes becoming patentable. This was exemplified by last year's ridiculous battle between Samsung and Apple on whether features like a rounded rectangular cellphone screen and finger movements were patentable…."

  2. Sadanand Patwardhan Says:

    Good points made, but the article misses on an important one. The patents are supposed to spur innovation by providing incentive to innovator through patent protection [time bound monopoly]. But evergreening has the opposite effect by allowing Rent Seeking on otherwise expired patents and thereby not creating pressure for further innovation.

  3. Sadanand Patwardhan Says:

    There is an unexpected endorsement of India's Supreme Court judgement form Boston Globe:India agreed to enforce patents in order to join the World Trade Organization but, conscious of its role as low-cost supplier, has traditionally set the bar higher for patent approval than most developed nations. It is, in part, a deliberate move to prevent evergreening by establishing that a fresh patent will only be approved if a drug maker can prove a modified version shows much improved efficacy over an existing compound. Novartis, the court said, did not.The United States, on the other hand, has loosened its patent qualifications since the 1980s, and while the number of patents for genuinely new pharmaceutical products has dwindled, the total number approved has more than doubled. Nearly two-thirds of drug patents approved from 1989 to 2000 were for incrementally modified, or evergreened, medicines, according to the National Institutes of Health Care Management.

  4. Sadanand Patwardhan Says:

    Author is wrong when he says "India's Efforts" because Indian government would be more than willing to trade away sovereignty for Foreign Direct Investment. But he has alerted us to a grave danger to which every Indian should be made aware., India’s efforts to preserve policy space so as to ensure access to medicines for all, both in India and in developing countries, is under threat.This is because of an obscure provision that the EU is seeking in its pending trade negotiations with India. Under the so-called investment clause, foreign IP investors, such as Novartis and Bayer, will be given rights to sue the Indian government directly whenever their expectations of profit are frustrated by government decisions and policies.Using loose standards such as minimum standards of treatment, indirect expropriation, and national treatment, transnational corporations will be able to claim that denying patents, granting oppositions, revoking patents, issuing compulsory licences and registering generics before patent expiration all violate their expectations for profit. unquote

  5. Sadanand Patwardhan Says:

    Novartis routinely resorts to Fraud. US Investigation.^^^The US government has sued Novartis Pharmaceuticals Corp, claiming it gave kickbacks to pharmacies to switch kidney transplant patients from competitors' drugs to its own.The civil health care fraud lawsuit in US District Court in Manhattan seeks unspecified damages and civil penalties for a scheme that the government said has been carried out since 2005. ^^^

  6. Sadanand Patwardhan Says:

    Following the Novartis Judgment by India's Supreme Court eschewing the artifice of "evergreening", India's Intellectual Property Appellate Board (IPAB)found identical artifice by GSK in its breast cancer drug, Tykerb, unsustainable.**IPAB upheld a patent granted on the original compound, or active pharmaceutical ingredient, lapatinib, citing innovative merit. As a result, a GSK spokesman said its medicine would remain subject to patent protection until 2019. The additional patent on the particular salt of lapatinib used in Tykerb, which has now been rejected, would have extended that protection to 2021.**

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