Reaping the Benefits of Genomic and Proteomic Research Intellectual Property Rights, Innovation, and Public Health (2006) / Chapter Skim
Currently Skimming:
2 Genomics, Proteomics, and the Changing Research Environment
2 Genomics, Proteomics, and the Changing Research Environment
Pages 32-69
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 32... ...
(with its many spin-offs, such as the SNP Consortium,1 the HapMap Project,2 and the Protein Structure Initiative) ,3 aims to provide a complete working knowledge of the human genome and, in the longer term, proteomics, which together will provide information and the tools necessary for advancing our understanding of human health and disease.
|
From page 33... ...
Open, facile access to this relatively limited amount of DNA sequence information became an important priority for molecular biologists and molecular geneticists alike. As a result, in 1979 GenBank was established as a nucleic acid sequence database at the Los Alamos National Laboratory and was funded by the National Institute of General Medical Sciences three years later.
|
From page 34... ...
by appropriating funds to both DOE and NIH for that specific purpose. As envisioned in the NRC report, the HGP did not begin immediately with human sequencing.
|
From page 35... ...
EST and cDNA sequencing also provided a rapid means of identifying and characterizing some medically significant genes, opening a path to early intellectual property claims. Venter pursued EST sequencing vigorously, and two companies, Incyte and Human Genome Sciences, devoted extensive resources to capturing these sequences and obtaining patent rights to them (see Chapter 3)
|
From page 36... ...
Genome sequences from species across the evolutionary tree continue to flood the databases today. HUMAN GENETIC VARIATION One of the most important uses of the human genome sequence information is its explanation of how DNA sequence variation leads to differences among
|
From page 37... ...
Alternative treatment strategies are aimed at trying to restore protein functions that have been lost as a consequence of mutations. For example, drugs that directly influence the functioning of mutant forms of the cystic fibrosis transmembrane conductance regulator protein are now going into clinical trials with the hope that they will be able to restore sufficient function to alleviate the devastating symptoms of cystic fibrosis.
|
From page 38... ...
In all, there are approximately 3 billion bases in the human genome, which means that the DNA sequences of any two individuals differ at more than 2,000,000 base positions along the DNA double helix. Among such differences are those that underlie heritable variation among individuals for an enormous number of traits, such as eye and skin color.
|
From page 39... ...
Simultaneous measurement of many mRNA levels now can reveal patterns of gene expression for an organism or a tissue under various conditions that can then be compared, pointing to genes characteristic of certain states or reactions. For example, distinct subtypes of large-cell lymphomas, with quite different responses to chemotherapy, can be distinguished from one another by measuring mRNA expression patterns, thereby providing a means of directing therapy (Staudt and Dave, 2005)
|
From page 40... ...
For example, muscle cells preferentially express the gene encoding the red-colored, oxygen-storage protein myoglobin at high levels, thereby ensuring that we can exercise. In contrast, skin cells strongly express the genes encoding the skin keratin proteins that provide the protective layer covering our bodies.
|
From page 41... ...
As the number of protein structures elucidated with x-ray crystallography and NMR increased, a need was perceived by the scientific community to archive the atomic coordinates (or positions) for each protein.
|
From page 42... ...
funding agency (the National Institute of General Medical Sciences) adopted guidelines published by the International Union of Crystallography requiringdata deposition for all three-dimensional protein structures.
|
From page 43... ...
For statistical reasons, relatively large populations will need to be studied to define the relative contributions of each change in the DNA sequence or degree of methylation, mRNA expression level or protein concentration, and degree of post-translational modification. The opportunity to create new intellectual property is rich, and it is possible that it will be difficult for one gene patent to block the development of these tests.
|
From page 44... ...
The Stevenson-Wydler Technology Act, which established basic federal technology transfer policies, enables NIH and other federal agencies to execute license agreements with commercial entities in order to promote the development of technologies discovered by government scientists. The act also provides a financial return to the public in the form of royalty payments and related fees.
|
From page 45... ...
Secrecy can be problematic for the careers of students and junior faculty members who must publish their research findings to establish their reputations and obtain funding. For this reason, most universities strive to file patent applications quickly so that publications are not delayed.
|
From page 46... ...
U.S. patent law provides a grace period enabling an inventor to disclose an invention -- for example, in a paper or conference presentation -- up to one year before filing a patent application.
|
From page 47... ...
Similarly, hemophiliacs had also contracted hepatitis when these viruses contaminated the blood pool. Recombinant human Factor VIII, approved in 1992, eliminated the constant problem of blood contamina tion and offers lifesaving benefits to hemophilia A patients (Kaufman, 1989)
|
From page 48... ...
Large-scale sequencers, such as Human Genome Sciences, Inc., de velop research databases of genes, gene fragments, or gene expression patterns, which enable drug discovery. Celera Genomics entered this field as it began its human genome sequencing.
|
From page 49... ...
SCIENTIFIC NORMS AND EVOLVING SCIENCE POLICIES Since the inception of the HGP, debates about access to data and information have remained ongoing. In addition, there have been disputes about the propriety of patenting genes, partial genes, or gene products, as well as disagreements in the research community about whether academic institutions should be encouraging patenting and licensing strategies versus facilitating open access to data and resources.
|
From page 50... ...
One reason for the remarkable success of science is the communal nature of scientific activity. Thus, undue restrictions on data, information, and materials derived from science, especially publicly funded science, has been a theme of many discussions in the science policy community over the past 20 years.
|
From page 51... ...
Combined with a genome sequence, an EST can provide a valuable clue to the presence of a gene in the genome. Generally, EST patent applications contain broad claims, and researchers typically have identified new ESTs, guessed at the biological function of the encoded protein fragments through computerized searches of the DNA and protein databases, and then sought utility patents on the proteins on grounds of hypothetical function.
|
From page 52... ...
ESTs may be novel, because the sequence has not yet been published. Further, ESTs may "enable and describe at least one use, as a DNA probe." The scientific community has expressed several concerns about the allowance of broad patent claims on ESTs, including: · whether a DNA sequence including well-studied genes later found to contain the EST sequence would infringe the patent on that EST sequence; · whether companies currently using gene sequences in clinical trials or those selling recombinant proteins could infringe on one or more EST patents and as a result be forced to re-engineer their gene sequence and repeat years of experiments to avoid the infringement; and · whether industry would delay or refrain from investing in genomic research and development due to uncertainty surrounding the scope of millions of secret EST claims at USPTO that have not yet been made public either by publication of the application or issuance of the patent itself.
|
From page 53... ...
Varmus and Collins appealed to USPTO for consideration, writing: While we were pleased with the PTO's new stance on the utility of polynucle otides for which only generic utilities are asserted, we were very concerned with the PTO's apparent willingness to grant claims to polynucleotides for which a theoretical function of the encoded protein serves as the sole basis of the as serted utility.9 Currently, many patent applications directed to ESTs are pending before USPTO. There have been persistent concerns that the patenting of an EST or indeed a gene without knowledge of its function, or with only a sketchy knowledge of its function, could preclude a product patent by some future party who discovers a much more detailed and significant functional role for that gene.
|
From page 54... ...
In July 2005 a three-judge panel of the U.S. Court of Appeals for the Federal Circuit upheld USPTO in rejecting an EST patent application by Monsanto Corporation (In re Fisher, No.
|
From page 55... ...
Word quickly spread through the laboratory and soon everyone had a platinum wire "pick." Within a few years, Brenner's postdoctoral fellows went off to establish their own laboratories, often in the United States. Feeling isolated and at a competitive disadvantage relative to their peers studying the better-established Drosophila, they found that communication with their colleagues in the larger Cambridge group and with other new worm laboratories proved critical for success of the next generation.
|
From page 56... ...
The Bermuda Rules In 1996, an international group of scientists, from both the public and private sectors, who were engaged in genomic DNA sequencing, passed a unanimous resolution, commonly referred to as the Bermuda rules, which stated that "all human genomic DNA sequence information, generated by centers funded for large-scale human sequencing, should be freely available in the public domain in
|
From page 57... ...
Primary Genomic Sequence Should Be in the Public Domain It was agreed that all human genomic sequence information, gener ated by centres funded for large-scale human sequencing, should be freely available and in the public domain in order to encourage research and development and to maximise its benefit to society. Primary Genomic Sequence Should Be Rapidly Released - Sequence assemblies should be released as soon as possible; in some centres, assemblies of greater than 1 Kb would be released auto matically on a daily basis.
|
From page 58... ...
Unlike the consensus leading to the Bermuda Rules governing the HGP, general agreement on the desirability of instantaneous release of all interim data produced by structural genomics efforts was a nonstarter at Airlie House and subsequent international meetings. As for the issue of structural data release described above, much of the resistance was fueled by perceptions that patents on protein structures could generate significant financial returns within Japan and Europe.
|
From page 59... ...
The principles apply to all NIH-funded entities and address biomedical materials, which are defined broadly to include cell lines, monoclonal antibodies, reagents, animal models, combinatorial chemistry libraries, clones and cloning tools, databases, and software (under some circumstances) .13 Sharing Biomedical Research Resources The 1999 principles were developed in response to complaints from researchers that restrictive terms in material transfer agreements14 were impeding the sharing of research resources.
|
From page 60... ...
c. Utilization, commercialization, and public availability of technologies that are useful primarily as research tools rarely require patent protection; further research, development, and private investment are not needed to realize their usefulness as research tools.
|
From page 61... ...
Regarding best practices in licensing research tools, the report recommends pursuing a nonexclusive licensing agreement whenever possible. If an exclusive license is necessary to encourage research and development by the private sector, however, then the license should be tailored to promote rapid development of as many aspects of the technology as possible.
|
From page 62... ...
This concern is more acute in the area of diagnostic tests than it is in therapeutic product development, which clearly benefits from the protections the patent system offers during prolonged periods of research and development. The patent and licensing policies for genetic testing that followed the discoveries of the BRCA1 and 2 genes, the Canavan disease (CD)
|
From page 63... ...
Myriad, in essence, now had a monopoly over diagnostic testing for BRCA1 and 2 familial breast cancer in the United States. Myriad Genetics began enforcing its patent claims against certain universities, a previously rare practice.
|
From page 64... ...
. The Canavan Disease Story Another aspect of the controversy around genetic testing addresses the rights of patients and families whose tissue donation enable the discovery of a disease gene and eventually development of a specific test for its presence.
|
From page 65... ...
. MCH came under severe criticism from patient advocacy groups and from a CD screening consortium that had been banned from performing genetic testing.
|
From page 66... ...
Accordingly, many groups collaborated to develop detailed guidelines for HD genetic testing. In all instances, the groups included HD family members, interdisciplinary health care professionals, and research scientists.
|
From page 67... ...
Even individuals who are symptomatic may not want their insurance to cover the test, because a positive test implicates other family members as having a genetic risk, who then become uninsurable. Genetic testing for HD can have profoundly catastrophic and irrevocable repercussions, as there is no treatment, prevention, or cure.
|
From page 68... ...
either enforce their patent rights to prevent others from performing genetic testing, or present prohibitively expensive terms under which others may perform genetic testing. Anecdotally, there are instances in which hospital laboratories performing tests on genes covered by patents have continued to offer the test until subjected to very strong pressure from the patent holder or exclusive licensee.
|
From page 69... ...
Because much of the intellectual capital in this area has resided in academic research institutions, the relationships among universities, government, and the private sector also have changed. Although these relationships have been highly beneficial, they also have generated debates about the relative roles of government and industry in supporting and promoting science, particularly with regard to open access to information and the sharing of research resources.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.