Mr. Lamb is a freelance pharmacy writer living in Virginia Beach, Virginia, and president of Thorough Cursor Inc.
The government of Thailand decided to issue compulsory licenses on Abbott Laboratories' lopinavir?ritonavir combinations Kaletra and Aluvia in January 2007.1,2 Because compulsory licenses do provide for some royalty payments to patent holders, however, they may prove to be more minor irritations than major crises for brand-name drug makers.
Shaping up to be much more problematic are administrative and legal decisions in some countries to revoke or deny patents on innovator drugs. When a country fails to grant or uphold a product's patent, manufacturers in that country can produce copies and sell them with little legal liability.
Cases involving Pfizer's patent on sildenafil (Viagra) in China and Novartis' application for a patent on imatinib mesylate (Gleevec) in India illustrate what is at stake.
China's State Intellectual and Patent Office (SIPO) granted Pfizer a patent on sildenafil in September 2001. The organization rescinded that patent in July 2004, ruling in favor of Chinese drug makers who claimed Pfizer failed to disclose enough information about sildenafil in its application. A Chinese court overturned SIPO's ruling and reinstated Pfizer's patent in June 2006.3,4
The case was just the most publicized instance of legal challenges by Chinese firms to Western companies' patents. An analyst estimated that 99% of Western medicines sold in China are copies of drugs still under patent elsewhere.3 A telling example of this is that GlaxoSmithKline was compelled by market factors and SIPO petitions to surrender its Chinese patent on rosiglitazone (Avandia) in 2004. Commenting on that event, Hou Dakun, a consultant for the pharmaceutical industry in China, said, "Any patent earning a huge profit in the market would spark heated disputes not only in China but all over the world. Drug makers are becoming increasingly aware of breaking the monopoly of international pharmaceutical giants."5
Such difficulties in protecting intellectual property led Yalei Sun, an analyst from Morgan, Lewis, & Bockis, LLP, to observe, "Without necessary patent protection, no pharmaceutical company will find it financially viable to invest in the Chinese market."3 Add in the large amount of outright drug counterfeiting in China?even a generally positive profile of China's emerging basic pharmaceutical research sector by correspondent Jean-Fran?ois Tremblay notes "respect for laws appears scant. Counterfeit drugs are widely sold in China"6?and it seems that companies that produce innovator drugs face great challenges in China.
The Chinese government did arrest hundreds of drug counterfeiters in August and September 2007 and executed a former director of China's drug safety agency for accepting bribes to allow fake and unsafe products onto the market.7,8 Despite these efforts, the US State Department has issued an intellectual property protection toolkit that notes, "Chinese authorities may want to consider making illegal all drug counterfeiting activities (including manufacture, sale,distribution, possession, and facilitation)."9
Patent security may be an even bigger issue in India than in China. India's modern pharmaceutical patent law was implemented in 2005 and, to date, very few of the more than 9000 drug patent applications submitted have been cleared.10
For the pharmaceutical industry, the most notable decision of the Controller General of Patents, Designs, and Trademarks is likely the January 2006 denial of Novartis' application for Gleevec. The Indian patent office invoked a clause of the country's Patents Act that prohibits the patenting of any drug product that was created before 1995, is a "derivative of known substances," or has not been proven more effective than an existing drug.11
The product Novartis applied for is a newer version of Gleevec that has been found in clinical use to have fewer adverse effects and greater bioavailability than the earlier version patented in several other countries besides India. Multiple generic copies of the older version of imatinib have been available from Indian companies for several years.
Norvartis challenged the denial on the grounds that the Patents Act provision went against the Indian constitution, which obligates the Indian government to abide by international treaties. As a signatory to World Trade Organization treaties, Novartis argued, India should be bound to patent any product that is novel, commercially viable, and nonobvious and blocked from adding additional barriers to patentability.
A high-level Indian court upheld the patent denial in August 2007, prompting Paul Herring, MD, head of corporate research at Novartis, to comment, "It is clear there are inadequacies in Indian patent law that will have negative consequences for patients and public health in India. Medical progress occurs through incremental innovation."12
Organizations such as M?dicines sans Fronti?res (MSF), however, welcomed the court's ruling because they interpreted it as one that will allow India to continue serving as the "pharmacy to the developing world."13 MSF estimates that some 80% of the HIV/AIDS drugs it distributes in Africa come from Indian manufacturers that produce both products tentatively approved by the FDA and products that can be made generically because they have no patents in India.
Gilead Sciences is also trying to overturn an Indian patent denial for its tenofovir disoproxil fumarate (Viread). The appeal has yet to be heard, but the company is already acting as if a patent would be unenforceable, granting voluntary licenses to make and export tenofovir to several Indian drug makers.14