Business, Government and Society

Pre-Market structures facilitating

business

Session 2
 Basic Facts:
What is Glivec and who made it?
• Glivec (imatinib mesylate)--produced by Novartis--prescribed for
Chronic Myeloid Leukemia.
• Imatinib--invented in the late 1990s by biochemist Nicholas,
Elisabeth Buchdunger and Jürg Zimmermann at Ciba-Geigy (which
later became Novartis).
• Its use to treat CML driven by oncologist Brian Druker of Oregon
Health & Science University (OHSU).
• Other major contributions to imatinib development:
– Carlo Gambacorti-Passerini, Italy,
– John Goldman, UK
– Charles Sawyers of Memorial Sloan-Kettering Cancer Center.
• Druker led the clinical trials confirming its efficacy in CML.
 Timeline: The Patent
• 1992: Swiss patent application filed on imanitib
• 1993: patents in EU, the US, and other countries .filed
• 1996: US and EU issued patents listing Jürg Zimmermann as the inventor.
• 1997: Novartis filed a new patent application in Switzerland on the beta
crystalline
– This is the actual form of the drug sold as Glivec;
• 1998: Novartis filed international patent applications claiming priority to
the 1997 filing.
• 1998: Patent application filed by Novartis in India.
– Novartis fought a seven-year battle, case went to the Indian Supreme Court.
• 2005: US patent granted.
 Glivec Case in a Nutshell
• Novartis filed an application for Glivec, in the beta crystalline
form of the salt.
• The Supreme Court affirmed India’s pharmaceutical patenting
is stricter than the US or the EU.
– Patent applicant must show new form is different from old form
& the modification results in an improvement in the treatment.
• The Supreme Court upheld the Indian patent office's rejection
of the patent.
• Novartis threatened to stop supplying India with new
medicines.
Invention: One Man Show or Team Work?
• For Glivec, no one challenged Zimmerman’s sole
inventorship.
• But did he do it alone?
– Legally, the law does not look at whose contribution/effort
towards the product was more or less.
• Innovation rests on the shoulder of giants
• Can we point to anyone person?
– Numerous scientists contributed to the making of Glivec
– Zimmerman and Buchdunger spent >2 years in developing the
right molecule
– Brian Drucker was the lead author of article on Glivec and
worked to find a treatment for CML
• Teams have multiple layers
 Glivec Case in India: Brief History
• The TRIPS 2005 Agreement set mandatory minimum rules for
20 year patents for products and processes
– The agreement did not stipulate what ‘new’ or ‘inventive’
– This gave flexibility to developing nations.
• Earlier patent law in India no product patents only process
patents
– Generic medicines.
– India net exporter of medicine by 1988.
• India complied with the TRIPS--introduced Exclusive Market
Rights (ERM) regime
• Parliament careful that Right to Health not be compromised by
the ‘Evergreening’
– Resulted in the famous Section 3 (d) of the patent law
 Section 3 (d)
• Section 3(d) of the Indian Patents Act, 1970:
“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.”
• Novartis challenged section 3(d)
• 5 pre-grant oppositions filed by Cancer Patients Aid
Association (CPAA) and 4 by Indian Generic Companies.
 Two sides of the Argument
Indian SC Novartis
• Accepted that the beta crystalline • Novartis contented the invention
form imatinib mesylate was new was novel, inventive and
and not obvious. industrially applicable.
• Noted that 30% increase in • Alleged 30% increase in bio-
bioavailability was in comparison
to the free-base form of imatinib availability in the beta crystalline
which was already known, form mesylate.
therefore this comparison was • Significant increase in efficacy.
inappropriate.
• In the context of Section 3(d):
“…not all advantageous or beneficial
properties that directly relate to
efficacy, which in case of
medicine…is its therapeutic efficacy.”
 How Novartis Reacted?
• Stated that imatinib mesylate had been granted patent in 40
different countries and India should do the same.

• Justified its patent claims by stating R&D costs need to be

recovered through the drug’s high cost.

• Tried to raise fears about the future of innovation in India if

patents were rejected.
Global Context: Negotiations at WTO
• In 1986: Uruguay round under the GATT.
• The developed countries introduced issues not entirely to
trade such as IPR, investment and services.
• Initially, the developing countries lead by India and Brazil able
to stall the introduction of these new issues.
• USA continued to press for inclusion
– Economy in a bad shape
– Losing competitive edge in manufacturing
– Agricultural exports threatened by state-subsidised agricultural from
Europe.
– Protecting IP-dependent industries where it still had an advantage –
Pharmaceuticals, software and audio-visual media.
 So Where is This Coming From?
Global Context: Negotiations at WTO

• India had a clear interest in not agreeing to these new demands

– Indian Patent Act, 1970 did not allow patents on medicines and agro-
chemicals; the Indian pharma sector had flourished.
• By the beginning of 1989, the resistance by developing
countries was broken down.
• The significance of the negotiations was not clear to most
popular movements and civil societies in different parts of the
world.
 Are Patents on Medicines Ethical?
• Evergreening and the practice of abusive patenting were first
highlighted in 1990s with the HIV epidemic, when medicines
were priced way out of reach.
• First example: ‘Zidovudine’ (AZT)-- a cancer drug, but GSK
granted a patent for it as a antiretroviral.
• GSK in 1977 granted secondary patent in several countries
making the access to this drug difficult and expensive for
patients.
 Are Patents on Medicines Ethical?
• India managed sustainable supply of affordable HIV
medication through generics manufacture.
• 1995: In anticipation of change in patent laws many patents
filed for TB, cancer, HIV drugs.
– Resulted in many secondary patent applications pending in the
Indian Patent office
• MSF, UNAIDS, WHO and French President warned India to
strike a balance between the TRIPS obligation and protecting
the access to affordable medicines.