User:Mac/The Problems of Patents on Diagnostic Testing Kits
Diagnostic kits are biotechnological tools that provide information about a patient's health by analyzing biological variables related to a particular biological state or outcome. Diagnostics exist for everything from healthy conditions like pregnancy to transient diseases like viral infection to chronic diseases like cancers and genetic disorders and utilize a wide variety of biochemical, cytogenic, and/or molecular methods to analyze samples of nucleic acids, chromosomes, proteins, metabolites, and other small molecules.[1]
Today, the most activity in the diagnostic kit market, and certainly the most controversy, is coming from genetic tests and the promise of personalized medicine.
Genetic testing originally was a tool for evaluating a person's risk of developing or passing on single-gene disorders, enabling early detection of inherited diseases or conditions. However, advancing knowledge of the human genomeâcoupled with rapidly evolving technologiesâis providing new opportunities to assess common, multifactorial disorders such as heart disease, diabetes, asthma, and mental illness, which likely involve multiple genes and environmental factors. Moreover, genetic testing increasingly is being developed for use in personalized medicine, for example, for targeted treatment selection, identification and quantification of treatment risks, monitoring of treatment effectiveness and prognosis, and personalized disease management. Thus, the number of tests being developed and used in clinical practice will increase over time. [3]
The types of patents most strongly associated with genetic tests based on DNA samples are "composition of matter/manufacture claims to isolated nucleic acid molecules (typically for molecules that are useful as probes against genetic markers); manufacture claims to genetic test kits; process claims to diagnosis through genetic testing; and manufacture claims to gene chips and microarrays."[4] Patents on isolated nucleic acid molecules and on diagnostic processes are referred to as "diagnostic methods".
Now I will briefly present two controversial diagnostic method patents and use them as a concrete, if somewhat extreme, basis for exploring the problems of patents on diagnostic testing kits.
Myriad Genetics was granted diagnostic method patents (both composition and method claims) on alleles of the BRCA1 and BRCA2 genes that indicate risk for breast and ovarian cancer in 1990. Myriad had previously conducted significant research to determine the clinical validity of a test based on the two alleles. The patent covered both sequencing a patients BRCA genes and comparing the results with the risky alleles. Currently it is the sole provider of BRCA1 and BRCA2 cancer diagnostics based on complete sequencing of the genes. However, as of the mid 1990's BRCA testing had become available through public laboratories via a less expensive 2-step method that involved analyzing the BRCA proteins and then doing limited sequencing. [6]
A more controversial diagnostic method patent was awarded to three medical school professors from the University of Colorado and eventually licensed to Metabolite Laboratories. The patent covered measuring the total concentration of homocysteine in a patient's bloodstream and correlating high levels with vitamin B-12 deficiency. This patent is controversial because Metabolite asserts licensing rights for the "process" of correlating high homocysteine levels with vitamin deficiency. Although other inventors might find another way of measuring homocysteine levels, there is only one way of doing the correlation, so Metabolite has a strong monopoly on the patent.
Metabolite licensed the diagnostic to LabCorp, whom later switched to a different vendor's kit to measure homocysteine level while continuing to promote the correlation method protected by Metabolite's patent to customers. Metabolite took them to court. LabCorp appealed, and they went all the way up to the Supreme Court. However, the Court encountered a technicality and didn't rule one way or the other.
These two cases present a startling aspect of diagnostic method patents: the strongest part of the patent are not the composition claims, but the process claims. While another inventor might be able to "engineer around" a particular material or manufacturing process, in principle a broad analysis or interpretation process claim could be impossible to reinvent.
Based on these two oversimplified case studies, here are several concerns about patents and diagnostics:
Concern 1. Diagnostic method patents with unique process claims may be impossible for other inventors to engineer around and consequently would amplify the effective monopoly granted to the patent holder. The patent holder would have absolute monopoly over the price, supply, and use of the diagnostic. If they elected to exclusively license the patent, patients and scientists might suffer because they wouldn't be able to seek a second opinion on the results of the diagnostic, or perform the diagnostic in alternate forms not offered by patent holder (i.e. neonatel).
Despite these concerns, previous studies of diagnostic kits in monopoly situations have not not found that they are consistently more expensive or worse in quality than non-exclusively licensed kits. [1, 2]
Concern 2. Ubiquitous genome sequencing will undermine the composition claims of diagnostic method patents, leaving only the unique process claims. When an individual has their genome sequenced, they may be incidentally infringing on certain composition claims of diagnostic methods based on sequencing particular genes. Even if not, it is imaginable that once the sequence data is in hand, it would be much easier to infringe on an process claim or patent, since the transaction cost would just involve analyzing the particular sequence data in the manner specified in the patent. Hence the falling costs of genomic sequencing technology, the ubiquity of computers, and the public disclosure of analytical methods in the patent application could combine to make infringement easier to do and harder to detect. This might be a source of pressure for owners of analytical processes patents to explore alternative strategies for monetizing their inventions, at the very least with broad, cheap licensing.
Concern 3. Many gene markers suspected of clinical relevance may be patented based on preliminary work, but never clinically investigated in trials. When patents have prevented other interested parties from running the trials themselves due to inordinate licensing costs, there have been calls for the construction of a commons for gene markers, organized by the government, that researchers would be free to investigate and collaborate on, similar to the Human Genome Project. [5] This could be a good candidate for further research.
Lastly, as our ability to sample biological systems becomes more powerful and less expensive, and our understanding of those systems becomes more complete, there will be growing opportunities to develop "multiplex" kits that use the state of hundreds or thousands of different parts of a biological system, beyond just nucleic acids, to make predictions about it. If each separate measurement technique is protected by different intellectual property, the transaction cost of licensing each for a high-throughput measurement kit might make commercialization impossible. This may be a reasonable concern in metabolomics if there is no standard "sequencing" reaction akin to those available for nucleic acid sequencing and each probe for detecting a particular metabolite from the metabolome is encumbered with its own IP.
Further research questions:
How common and how strong are process patents for most diagnostics (not just the crazy extremes)?
Are there any existing multiplex diagnostics? How are the individual probes or tests licensed? Is there an opportunity for promoting a commons approach?
What are the basic stats of the Diagnostic Kit subsector: market cap, top 10 most profitable kits, typical lifecycle and development cost.
References
[1] U.S. System of Oversight of Genetic Testing: A Response to the Charge of the Secretary of Health and Human Services. (http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_oversight_report.pdf)
pg 53. Types of Genetic tests
[2] The dangers of diagnostic monopolies (http://www.nature.com/nature/journal/v458/n7237/full/458405a.html)
[3] U.S. System of Oversight of Genetic Testing: A Response to the Charge of the Secretary of Health and Human Services. (http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_oversight_report.pdf) pg 1.
[4] U.S. System of Oversight of Genetic Testing: A Response to the Charge of the Secretary of Health and Human Services. (http://oba.od.nih.gov/oba/SACGHS/reports/SACGHS_oversight_report.pdf)
pg 34.
[5] What's the Point in Patenting Genes? (http://beta.technologyreview.com/biomedicine/22704/page1/)
[6] History of a gene patent: tracing the development and application of commercial BRCA testing. (http://www.ncbi.nlm.nih.gov/pubmed/14748275)
[7] Laboratory Corporation of America Holdings v. Metabolite Laboratories, Inc. and Competitive Technologies, Inc. (http://topics.law.cornell.edu/supct/cert/04-607)