Multiple/conflicting IP ownership will lead to multiple access requirements and this, in turn, can create significal technology access problems. An extreme example is that of agricultural biotechnology and vitamin A golden rice which is made using recombinant DNA technology. Each plant contains several exogenous DNA fragments that allow the plant to synthesize large amounts of Vitamin A⁴. Depending upon the country, between zero and 40 (!) separate patents need to be accessed in order to create a “golden rice” plantⁱ.

ⁱ Kryder, RD. Kowalski, SP. & Krattinger, AF. (2000), The intellectual and property components of pro-vitamin A rice (Golden Rice): A preliminary freedom to operate review, ISAAA Briefs No. 20.

The “anticommons” barrier to improved availability of FDCs revolves around IPRs of the individual FDC components, exemplified by the antiretroviral FDCs. Trizivir ®, approved by the FDA in November 2000 for the treatment of HIV in adults and adolescents, is an FDC of Ziagen® (abacavir sulfate 300mg/ABC), Retrovir® (zidovudine 300mg/AZT), and Epivir® (lamivudine 150mg/3TC). Ziagen® was discovered and is being developed by GlaxoSmithKline and all rights to technology, including intermediates used in its were licensed to Glaxo Wellcome by the University of Minnesota in 1992. Lamivudine was discovered by BioChem Pharma of Laval, Quebec, Canada and licensed to Glaxo Wellcome in 1990. GlaxoSmithKline therefore has outright intellectual property ownership or exclusive rights to all components of Trizivir®. CIPLA, Ltd, the Indian drug company, makes an FDC (“Triomune”) which contains nevirapine, stavudine (d4T) and lamivudine (3TC). Each component is owned by a different party; Yale (stavudine), BioPharma/Glaxo (lamivudine) and Boehringer Ingelheim (nevirapine)^5,ii. Thus, even if components of FDCs may be patented separately and owned by different parties or all components may be owned by the same party, requiring a license to even one component of an FDC is enough to block access to the whole.

ⁱⁱ ISAAA, USA. (http://www.agbiotechnet.com). ii India can manufacture these antiretrovirals domestically because its patent system, albeit only until 2005, only allows pharmaceutical method of manufacture patents. India can “design around” method patents by making them using a different method than that described in the patent.

Table 1 lists the components of these FDCs (column 3: Triomune; column 4: Trizivir®). Data from Attaran and Gillespie White⁶ allows us to list those countries that have patent protection for all three components of the particular FDC (“+++”) or just individual components. We note that Combivir® is an FDC of lamivudine and zidovudine. Thus, the presence of patent protection for a Combivir® product might also effectively block production, sale, or use of Trizivir®®, since Trizivir® contains within it the components of Combivir®. Even if the healthcare systems in the countries of Table 1 were entirely efficient in delivering medicines (which they are clearly not), the blockage of these FDCs by IPRs affects tens of millions of people. Table 1 lists the prevalence of HIV+ adults affected by this lack of FDC access⁷. In this regard, Aspen has received a voluntary license for the components of Trizivir® and recently received a voluntary license (terms unknown) apparently allowing it access to nevirapine and and stavudine. The terms of the license are such that FDCs can be made from these two components (Richard Laing, personal communication, 10 November 2003).

Table 1: Components of various FDCs that are patented in selected African countries

+++ signifies that all three components are under patent (as of 2001)
Data in column 2 are as of the end of 1999 (Source^vii)

Fortunately, the major components of FDCs for tuberculosis are off patent but the problem will resurface as new TB drugs become available and anti-mycobacterial resistance to existing drugs increasesⁱ. With regard to patented malaria FDCs, one example is Coartem, marketed by Novartis. This patented FDC (artemether/lumefantrine) is being provided at cost by Novartis and distributed through the WHO as part of the worldwide Roll Back Malaria initiative. Coartem contains the same ingredients as far more expensive Riamet, a Novartis medication approved in Europe for travellers visiting malaria-endemic regions. The incentives for a third party (i.e., a generics manufacturer in India) to make Coartem at a profit are necessarily undercut since Novartis is selling the drug at zero margin.

ⁱ In the US at least, there exist multiple incentives to stimulate the development of antimicrobial agents. They include orphan drug exclusivity (James Love Comments on the Orphan Drug Act and Government Sponsored Monopolies for Marketing Pharmaceutical Drugs. United States Senate, Committee on the Judiciary, Subcommittee on Antitrust, Monopolies and Business Rights, Anticompetitive Abuse of the Orphan Drug Act: Invitation to High Prices, January 21, 1992, Serial Number J-102-48, pages 259-283), the Waxman-Hatch initiative (Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585, codified at 15 U.S.C. §§ 68b-68c, 70b, 1994), pediatric exclusivity (see, for example, the FDA’s report (htpp://www.fda.gov/cder/pediatric/reportcong01.pdf), a certain prioritization for expedited review of agents effective for certain resistant organisms, higher consideration for expedited review of drugs in new classes with novel mechanisms of action, and federally funded clinical study groups. Most pharmaceutical companies are aware of these incentives and utilize them although for some of these intiatives, the public health consequences are far from clear. However, the real problem is that there is significantly diminishing FDA submissions and diminishing approvals of newer antimicrobials.