Recent advances in the ability to engineer customized zinc-finger proteins (ZFPs), which can bind virtually any DNA sequence of interest, have generated excitement among both academic and industrial researchers. Engineered ZFPs can be used to alter chromatin structure, regulate endogenous gene expression levels, and introduce targeted modifications in genes. In one salient case, a chimeric zinc finger–nuclease (ZFN) successfully stimulated homologous recombination and thus repaired a mutant IL2R γ (IL2RG) gene associated with X-linked severe combined immune deficiency (SCID) (1). ZFP-based therapeutics developed by Sangamo Biosciences for diabetic neuropathy and peripheral arterial disease are undergoing phase 1 and 2 clinical trials (2), and a ZFN-mediated approach for disrupting the CCR5 receptor in patient T cells as a strategy to increase resistance to HIV is in preclinical development (3). These advances have given researchers hope that ZFP- and ZFN-based approaches may help improve both the efficiency and the precision of gene therapy. Other potential commercial applications for ZFPs include plant genetic engineering, the production of biopharmaceutical molecules such as growth factors and antibodies, and the nascent field of synthetic biology. ZFN technology has also been used successfully to make targeted gene modifications in several model organisms such as Drosophila (4), C. elegans (6), plants (7,8) and most recently zebrafish (9,10), illustrating the range of uses for ZFNs in basic research as powerful molecular biology tools.
As might be expected with any research platform that has many potential commercial uses, a large patent estate now covers both the engineering and the use of ZFPs. Notably, the patent estate was initially owned by several different companies and academic institutions, thereby creating the possibility that subsequent users and developers would face prohibitive costs in negotiating multiple licenses—the classic scenario of a patent "anticommons" (11). However, one company, Sangamo, has now consolidated the majority of this patent estate. The dominant patent position held by Sangamo has raised the recurrent question of whether a company's monopoly control over an important and versatile research platform will ultimately help or hinder optimal development of that platform. Because such development can occur within both the private and public sectors, there is also the subsidiary issue of whether patents will be enforced against academic researchers in the same manner as they might be enforced against private-sector competitors.
Previous studies (12) suggest that academic researchers do not seem concerned about being sued by private-sector patentees. For example, a survey of academic biomedical researchers found that only 5% report checking for patents related to their research (13). These studies further indicate that private-sector patent owners practice "rational forbearance" and do not sue academic researchers because of the difficulties and disadvantages of asserting patent rights in such circumstances (14, 15). Currently, the conventional view is that academic biomedical research is more likely to be impeded by lack of access to privately held research inputs such as materials, data and know-how than by patents (12, 13, 16, 17).
To explore the impact of ZFP patents, and specifically Sangamo's dominant patent position, on academic and commercial research and development, we systematically created a map of existing patents in the ZFP arena, presented here for the first time. We also conducted interviews with academic researchers in the field to develop a nuanced understanding of the complex interactions between private and public ZFP research endeavors. Our findings are consistent with the view that, for academics, lack of access to information and materials is a greater problem than the threat of patent lawsuits. However, because some of the access problems would have been alleviated if statutory obligations regarding patent disclosure had been met, our research also suggests the heretofore unrecognized possibility of an overlap between patents and access to information and research materials. More complete patent disclosure might also have obviated the need to generate various open-science alternatives to the Sangamo platform.