In his charge to the committee at its first meeting, Francis Collins, Director, National Human Genome Research Institute, requested data on what patents have been issued or applied for, by whom, and in which countries for nine more specific categories of genomic- and protein-related patents: gene regulatory sequences, single nucleotide polymorphisms (SNPs) and haplotypes, protein structures, protein-protein interactions, gene expression profiling, genetically modified organisms, and related software, algorithms, and databases.

Further discussions among the committee resulted in the selection of three additional patent categories, each representing a distinct disease-related molecular pathway: Cytotoxic T-Lymphocyte Associated Protein-4 (CTLA4), Epidermal Growth Factor (EGF), and Nuclear factor-Kappa B (NF-kB).5 CTLA4, EGF, and NF-kB were chosen from a longer list of known pathways on the basis of four criteria:

  1. they are seen as involved in or correlated with more than one category of disease, spanning cancer and autoimmune or inflammatory diseases;

  2. there is significant scientific research interest, as indicated by frequent citation in the scientific literature;

  3. they exhibit some variance in the number of related patents; and

  4. there is some but varying industry involvement, represented by pharmaceutical or biotechnology firm patenting activity, licensing of university patents, or clinical testing or even marketing of therapeutic products.

5  

The following description is based on Walsh, et al., 2005. The biological pathways regulated by EGF, CTLA-4, and NF-kB are recognized widely by the biomedical research community for their roles in mediating disease and normal development. Stimulation of cells with EGF, for example, has been shown to induce cell division, an event that, if left unchecked, can lead to cancerous growth. The CTLA-4 receptor is involved in regulating T cell proliferation, and its loss of function is believed to contribute to autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and lupus. NF-kB also has been implicated in rheumatoid arthritis as well as asthma, septic shock, and cancer, and its role in the proper development and function of the immune system is supported by numerous studies of NF-kB knockout and transgenic mice.

The intense interest of the scientific community in these pathways is reflected in scientific publications and in the patenting of composition of matter products and/or processes related to EGF, CTLA-4, and NF-kB. Foundational papers on EGFand NF-kB each have been cited more than 1,500 times, while the more recent discovery of the functions of CTLA-4 has yielded more than 900 citations. Since 1995, USPTO has granted more than 760 EGF-related patents, 90 NF-kB patents, and more than 60 CTLA-4 patents distributed among large pharmaceutical firms, biotechnology firms, universities, and the federal government.

There are also on the market or in development several therapeutic products targeted to these proteins. For example, both Erbitux® (ImClone/Bristol-Myers Squibb) and Iressa® (AstraZeneca) are used for the treatment of cancers associated with EGF receptor expression. CTLA4-Ig® (Repligen) and Abatacept® (Bristol-Myers Squibb) also are patented and currently are in clinical trials for the treatment of multiple sclerosis and rheumatoid arthritis, respectively.



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