• Abstract and Figures
• Public Full-text

ARTICLE Impact of gene patents and licensing practices on access to genetic testing for long QT syndrome Misha Angrist, PhD, Subhashini Chandrasekharan, PhD, Christopher Heaney, BA, and Robert Cook-Deegan, MD Abstract: Genetic testing for long QT syndrome exemplifies patenting is important because knowing which gene (and which and exclusive licensing with different outcomes at different times. part of that gene) is mutated can have a direct bearing on Exclusive licensing from the University of Utah changed the business decisions regarding preventive measures and pharmaco- model from sole provider to two US providers of long QT syndrome logical therapies. testing. Long QT syndrome is associated with mutations in many genes, ● The major LQTS susceptibility genes were discovered 12 of which are now tested by two competing firms in the United States, at the University of Utah in the mid-1990s. Their dis- PGxHealth and GeneDx. Until 2009, PGxHealth was the sole provider, covery was funded in part by the National Institutes of based largely on exclusive rights to patents from the University of Utah Health. The first LQTS gene patent was awarded in and elsewhere. University of Utah patents were initially licensed to 1997. DNA Sciences, whose patent rights were acquired by Genaissance, and ● The University of Utah Research Foundation began then by Clinical Data, Inc., which owns PGxHealth. In 2002, DNA licensing patents on LQTS susceptibility genes in the Sciences, Inc., “cleared the market” by sending cease-and-desist patent late 1990s. Until recently, at any one time, there was enforcement letters to university and reference laboratories offering never more than a single licensee of the major intellec- long QT syndrome genetic testing. There was no test on the market for tual property (IP) attached to the three genes that pre- a 1- to 2-year period. From 2005–2008, most long QT syndrome-related dispose to the majority of familial LQTS. In 2008, patents were controlled by Clinical Data, Inc., and its subsidiary PGx- Bio-Reference Laboratories (BRLI) obtained an exclu- Health. Bio-Reference Laboratories, Inc., secured countervailing exclu- sive license for one of those patents and also for two sive patent rights starting in 2006, also from the University of Utah, and others, giving it rights to test for LQT3, which accounts broke the PGxHealth monopoly in early 2009, creating a duopoly for for ϳ10–15% of inherited LQTS. BRLI has since ag- genetic testing in the United States and expanding the number of genes gregated IP related to susceptibility genes for other for which commercial testing is available from 5 to 12. Genet Med forms of LQTS. As a consequence, the patent landscape 2010:12(4):S111–S154. for LQTS testing has become fragmented between 2 Key Words: patents, intellectual property, long QT syndrome, arrhyth- different exclusive licensees. mia, University of Utah, genetic testing ● In 2002, before a commercial test of five genes was launched under the name FAMILION®, there were at least two other fee-for-service providers of genetic testing; how- ever, they focused their sequencing on regions previously EXECUTIVE SUMMARY associated with mutations causing LQTS, which amounted to a minority of the five genes’ combined coding sequence. ● Familial long QT syndrome (LQTS) affects 1 in 3000 Subsequent enforcement of the gene patents prompted at newborns. It is a Mendelian condition in which patients’ least one diagnostic provider, GeneDx (subsequently ac- hearts do not recharge appropriately after heartbeats and quired by BRLI), to cease testing in 2002. We suggest that, can lead to life-threatening arrhythmias. It accounts for a based on incomplete evidence, this probably had a small small but significant fraction of sudden death in young but tangible negative effect on patient access to genetic people. Beta-blocker drugs and implantable cardioverter testing for LQTS between 2002 and 2004. We believe this defibrillators are the most common therapies. Patients and negative effect would likely have been larger had there those close to them can also endeavor to avoid triggers for been greater awareness, understanding, and acceptance of arrhythmias such as loud noises or physical or emotional genetic testing on the part of cardiologists and electro- stress. physiologists at that time. ● Mutations in 12 susceptibility genes account for some ● From 2005–2008, most LQTS gene IP relevant to clinical 75% of familial LQTS; of that 75%, mutations in three genetic testing was controlled by Clinical Data, Inc., and genes account for most cases. Genetic testing for LQTS its subsidiary, PGxHealth LLC. During that period, the company did not sublicense its test to any other diagnostic services in the United States, although it has granted in- From the Center for Public Genomics, Center for Genome Ethics, Law and ternational licenses in Australia, New Zealand, and Eu- Policy, Institute for Genome Sciences and Policy, Duke University, Durham, rope. It has also granted a research license to a company in North Carolina. Utah. Robert Cook-Deegan, MD, Center for Genome Ethics, Law and Policy, ● In general, clinicians whom we spoke to say that Institute for Genome Sciences and Policy, Duke University, Box 90141, PGxHealth does a very good job of performing genetic Durham, NC 27708. E-mail: [email protected]. testing of the five genes that account for ϳ75% of LQTS. Disclosure: The authors declare no conflict of interest. See Acknowledgments Its turnaround time for a complex, sequence-based test is for details. typically less than 2 months versus what is often a year or DOI: 10.1097/GIM.0b013e3181d68293 more for research-based testing. The company reports that Genetics IN Medicine • Volume 12, Number 4, April 2010 Supplement S111 Angrist et al. Genetics IN Medicine • Volume 12, Number 4, April 2010 Supplement its turnaround time has been substantially reduced since it evidence that PGxHealth is less (or more) adept at per- began offering the test. PGxHealth’s FAMILION testing forming this procedure than other commercial diagnostic continues to be widely adopted by cardiologists and elec- laboratories. trophysiologists, which the company attributes to its ef- ● Until 2009, PGxHealth tested just five genes in its LQTS forts to educate physicians and patients, its customer ser- testing panel, citing both minimal benefit in light of the vice, and diligent advocacy for reimbursement policies and rarity of mutations in the 7 other genes known to predis- payment agreement with insurers and health plans. It can pose to LQTS and uncertain clinical interpretation of un- be argued that (and has been by PGxHealth parent Clinical characterized background variants in these genes. When Data) an exclusive license has contributed to the compa- GeneDx secured exclusive rights on LQTS genes and entered the market, PGxHealth also expanded its testing to ny’s skill at performing the test and allowed it to leverage more than ten genes. economies of scale. GeneDx parent company BRLI at- ● Patients who were not found to have a mutation in the tributes these improvements to the march of technology genes included in the panel were referred to research and the threat of competition. laboratories for additional testing. Research laboratories, ● PGxHealth has been criticized for occasional laboratory however, may take months or years to return results. errors (missed mutations and misinterpretations). It is Although it is possible that sublicensing of the right to test not clear that the laboratory’s error rate is outside ac- the major genes would have made other providers more ceptable norms, or worse than its stated analytical ac- willing to assume the burden of testing the rarer loci, we curacy of Ͼ99%. PGxHealth says it implements process cannot know this. changes to ensure that any errors are not repeated, thus ● The recent acquisition of selected LQTS gene patent li- leading to improved accuracy over time. Misinterpreta- censes by BRLI may offer a real-world test of how prices tion, the company says, can be a subjective phenomenon respond to competition and of whether testing technology in a complex disease such as LQTS. PGxHealth consults changes with competition, although the nature of the com- with experts in the field to review variants of question- petition may not be head-to-head for the same mutations able interpretation. It also issues amended reports when unless a cross-licensing arrangement is struck between the interpretations change because of new knowledge in the rival testing services. field. ● Newer technologies minimize the cost of adding new mu- ● PGxHealth performs proficiency testing in conjunction tations, but without competition, the commercial incentive with Michael Ackerman, a researcher and physician at the to find new platforms is reduced. ● Mayo Clinic who has the sequencing facilities and diverse PGxHealth does not offer prenatal genetic diagnosis for genetic samples and clinical profiles necessary to conduct LQTS, effectively making it unavailable in the United States prior to 2009. The company does not have an such a program in accordance with the relatively nonspe- official policy governing prenatal diagnosis. It claims that cific regulations set forth by the CLIA, the pertinent fed- there are technical difficulties in distinguishing maternal eral statute. By all accounts, Dr. Ackerman is an outstand- from fetal DNA; however, other clinicians and would-be ing clinician and researcher who has greatly advanced the LQTS genetic test providers argue that this technical issue cause and treatment of LQTS patients. His financial ar- is trivial. At least one other former competitor has claimed rangements with Clinical Data and PGxHealth have been that the company denied its request to offer prenatal test- reported to and vetted by Mayo, and his service as a ing. Given the treatable nature of LQTS and the highly consultant to PGxHealth has been disclosed in publica- variable phenotype, it is not clear how strong the demand tions. would be for prenatal or preimplantation testing.

Load more

  44

Copy Link