High court decision in 2012 altered patent law and effectively blocked protections for certain clinical laboratory diagnostic tests and procedures
Clinical laboratory leaders and pathologists will be interested to learn that a US Supreme Court (SCOTUS) decision from 2012 may be partly to blame for the shortage of at-home COVID-19 rapid antigen tests while the SARS-CoV-2 Omicron variant surged this past winter.
During that time, consumer demand for all COVID-19 at-home tests quickly depleted the already dwindling supply. However, the 2012 SCOTUS ruling in Mayo Collaborative Services v. Prometheus—which rewrote patent law in the biotech industry—effectively blocked patent protections for many medical laboratory diagnostic tests and procedures, wrote Paul R. Michel in a column he penned for STAT.
Michel served on the United States Court of Appeals for the Federal Circuit from 1988 to his retirement in 2010, and formerly was its chief judge from 2004 to 2010.
Shortage of COVID-19 Home Tests Due to ‘Tsunami of Demand’
The diagnostic test shortage that continued throughout the second year of the pandemic has been blamed on a “tsunami of demand,” as vaccine and testing mandates went into effect, according to CNBC. Other causes of the shortages were linked to shortages of raw materials and the US Food and Drug Administration’s slow review process, The Wall Street Journal reported.
However, as Michel noted in STAT, Mayo v. Prometheus “was a legal bombshell that upended the prior law on patent eligibility. And it has had disastrous real-world consequences for Americans.”
San Diego-based Prometheus Laboratories had developed a diagnostic test that measured how well patients metabolized medicines to treat autoimmune diseases. When Mayo Collective Services, which does business as Mayo Clinic Laboratories, developed its own test based on the Prometheus design, Prometheus sued for patent infringement. But it lost when the case reached the Supreme Court.
Michel points out that developing new clinical laboratory diagnostic tests and methods is “slow and expensive” work that becomes financially unsustainable for biotech companies when patent protections are removed.
In the “wake of the Mayo decision,” he wrote, many small biotech companies that had been focused on developing new diagnostics went out of business. Simultaneously, some major research centers, such as the Cleveland Clinic, ended programs aimed at discovering new diagnostic methods.
Financial Repercussions of the SCOTUS Ruling
“In essence, in the four years following Mayo, investment in disease diagnostic technologies was nearly $9.3 billion dollars lower than it would have been absent Mayo,” wrote A. Sasha Hoyt, in her analysis of financial repercussions caused by the loss of venture capital investment in new medical laboratory diagnostics. Hoyt is an incoming associate and judicial extern at Finnegan, Henderson, Farabow, Garrett and Dunner, LLP in Washington DC.
“However,” she added, “it is important to note that the yearly investment totals for disease diagnostic technologies have generally increased in the years following Mayo—but it has increased at a lower rate compared to all other industries.”
Shahrokh Falati, PhD, JD, director of the Patent Law Clinic at New York Law School, maintains that the Supreme Court-created exceptions to existing patent law have damaged America’s standing as a leader in new technology development and commercialization.
“The US Supreme Court effectively redefined the scope of patent eligible subject matter when it decided Mayo. This decision focused on medical diagnostic technology and has had a profound effect on the biotechnology and personalized medicine industries in the United States …,” he wrote in the North Carolina Journal of Law and Technology.
“[The Supreme Court’s ruling] has caused havoc in the biopharmaceutical industry by not only making it a near impossibility to obtain a patent in certain fields, but also by vastly increasing the number of medical diagnostic patents being invalidated based on Section 101 of Title 35 of the US Code,” said Shahrokh Falati, PhD, JD (above), director of the Patent Law Clinic at New York Law School, in an article he wrote for the North Carolina Journal of Law and Technology. Funding for clinical laboratory diagnostics development also has curtailed since the SCOTUS ruling. (Photo copyright: Albany Law School.)
Precision Medicine at Risk without Intellectual Property Protection
Elizabeth O’Day, PhD, CEO and founder of Olaris, Inc., a precision medicine company, has advocated for reform of Section 101. In an Olaris blog post, she argues that reform should provide intellectual property protection for therapeutic companies that develop biomarkers and algorithms used in precision medicine.
“We have the omic technologies (genomic, proteomic, metabolomic, etc.) and analytical tools needed to uncover biomarkers that could dramatically enhance our ability to detect and treat disease,” O’Day wrote. “Let’s reform Section 101 so that these breakthrough products have the opportunity to reach the people that need them.”
In, “CMS Cuts BRCA Price by 49% in Response to Competition,” Dark Daily’s sister publication, The Dark Report, highlighted the negative consequences the Mayo decision had on the clinical laboratory diagnostic testing industry.
“It is past time that Congress act to address this issue,” they wrote. “To assist us as we consider what legislative action should be taken to reform our eligibility laws, we ask that you publish a request for information on the current state of patent eligibility jurisprudence in the United States, evaluate the responses, and provide us with a detailed summary of your findings.” That letter went to Hirshfeld on March 5, 2021, with a request for findings no later than March 5, 2022.
For now, patent reform appears to be locked in uncertainty, which means SCOTUS’ decision that altered patent law affecting the biotech industry may continue to hamper development of new diagnostic tests as well as the current supply of at-home COVID-19 tests. Clinical laboratory leaders involved with diagnostic test developers will want to closely monitor for any changes to the Supreme Court’s ruling.
Drone program will enable delivery of medical laboratory samples during the day, rather than just at night, allowing daytime sample processing that will increase efficiency and shorten time to results
Healthcare network clinical laboratories continue to explore the use of unmanned aerial vehicles (UAVs), commonly known as drones, to safely deliver medical supplies and clinical laboratory specimens between locations. Dark Daily has covered several similar pioneering drone programs taking place around the world in recent years.
The latest medical laboratory company to launch a drone delivery program is Interpath Laboratory, an independent full-service medical laboratory in the Pacific Northwest.
In partnership with Arizona-based Spright—the drone division of Air Methods, a patient transport company with 300 bases in 48 states—Interpath recently announced the launch of its drone delivery pilot program for delivering lab testing specimens from Yellowhawk Tribal Health Center to Interpath’s medical laboratory in Pendleton, Oregon.
The two organizations hope the initiative will expedite the turnaround time needed for test results, thus allowing for timelier diagnoses and improving patient care and outcomes.
“Many communities located in remote or rural areas lack timely and convenient access to essential medical supplies and service,” said Joe Resnik (above), president of Spright in a press release. “We look forward to this proof-of-concept, showcasing drone delivery’s ability to solve many of healthcare’s existing access and efficiency challenges, while also improving patient care and experience.” (Photo copyright: KVS Technologies.)
Replacing Automobile-based Medical Laboratory Specimen Delivery
“If this pilot program is successful and we are able to utilize this service, our patients have the opportunity to benefit from more rapid test results and access follow-up medical procedures and services,” stated Aaron Hines, CEO of Yellowhawk Tribal Health Center in a press release. “This project could help us further our mission of providing high-quality, primary healthcare for the Confederated Tribes of the Umatilla Indian Reservation (CTUIR).”
Currently, patient samples taken throughout the day at various Yellowhawk facilities are picked up and delivered to Interpath’s clinical laboratory in the evening via gasoline-powered vehicles. A successful drone service would allow lab test specimens to be repeatedly picked up and delivered to the lab for analysis throughout the day.
“Medical laboratory services in rural areas frequently must invest intensive time and resources into sample pick-up,” said Tom Kennedy, president of Interpath Laboratory, in the press release. “We anticipate Spright’s drone delivery service will alleviate many of the drawbacks and costs associated with automobile-based delivery. This initiative represents an example of our embrace of innovative solutions that provide more efficient and effective services to our clients.”
In February, Spright held test flights that transported clinical laboratory specimens from Yellowhawk Tribal Health Center to Interpath’s main medical laboratory in Pendleton, Ore. The 15-mile flight used a Wingcopter 198 drone (above) which employs beyond-visual-line-of-sight (BVLOS) technology. Manufactured in Germany, the Wingcopter 198 has a wingspan of five feet ten inches and can carry up to 13 pounds. It has a range of 46 to 68 miles, and a maximum speed of approximately 62 to 90 miles per hour, depending on the weight of its load. (Photo copyright: sUAS News.)
Other Clinical Laboratory Drone Deliver Programs Worldwide
Innovative approaches, such as the utilization of drones to make clinical laboratory specimen deliveries, can help circumvent many of the challenges in delivering healthcare to rural areas. But UAV delivery networks work equally well for faster specimen transferals in urban environments as well, leading to timelier diagnoses of diseases and ultimately to better patient outcomes.
Though response was limited in Dark Daily’s poll, the message from respondents was overwhelmingly negative on LDT regulation by the FDA
Most respondents to a recent industry survey said that should Food and Drug Administration (FDA) approval be required in the future for laboratory developed tests (LDTs), innovation will suffer.
In the survey, which was conducted by Dark Daily, 91% of respondents said FDA pre-market approval of LDTs would decrease clinical laboratories’ ability to bring innovative tests to market. (See Figure 1.) The other 9% felt it would have no effect on innovation. Zero of the respondents said FDA involvement would increase innovative tests.
Figure 1: “How might a requirement of FDA pre-market approval impact the ability of your lab (or a lab you work for) to bring innovative tests to market?“
“Development of LDT tests has been the mission of most of the labs, and it meets the need for patient care,” noted one respondent in the survey. “Moving LDTs under FDA will create more obstacles for labs to offer the tests.”
To be fair, the survey had limited responses—34 in total. The poll went out to thousands of Dark Daily readers. We found that response rate surprising given how many labs will be affected if the VALID Act becomes law.
The VALID Act is a bipartisan bill that proposes FDA oversight of laboratory developed tests. The bill continues to make its way through the U.S. Senate and the House of Representatives.
A counterproposal called the Verified Innovative Testing in American Laboratories Act (VITAL Act) is also before Congress but has less momentum behind it. The VITAL Act seeks to keep LDTs under CLIA while also calling for reforms to account for modern lab tests.
Looking at survey results, 80% “strongly disagreed” or “disagreed” that new LDT requirements, such as those found in the VALID Act, are needed. (See Figure 2.)
Figure 2: “FDA pre-market approval of LDTs should be required, as proposed in the VALID Act.”
By comparison, 65% “strongly agreed” or “agreed” with modernizing CLIA requirements for LDTs, as called for in the VITAL Act.
Those numbers shifted somewhat depending on the lab setting of the respondent. For example, just looking at commercial labs, opposition to the VALID Act remained similar, but support for modernizing CLIA jumped up to 88%. When looking at just hospitals, independent labs, and academic labs, numbers for both topics remained consistent.
When filtering the answers, the number of lab employees in a setting had little effect on survey results.
Political Battle Continues Over Laboratory Developed Tests
Clinical laboratory industry groups and others have been amassing to oppose or support the VALID Act. For example, the Advanced Medical Technology Association and The Pew Charitable Trusts are behind the bill.
However, the American Association for Clinical Chemistry, Association for Molecular Pathology, and new Coalition for Innovative Laboratory Testing are against the VALID Act.
Should the test prove clinically viable, it could lead to new biomarkers for eye disease diagnostics and a new assay for clinical laboratories
Scientists at Flinders University in Australia have developed a genetic blood or saliva test that, they say, is 15 times more effective at identifying individuals at high risk of glaucoma than current medical laboratory tests.
If so, this discovery could lead to new biomarkers for diagnostic blood tests that help medical professionals identify and treat various diseases of the eye. Their test also can be performed on saliva samples. The researchers plan to launch a company later in 2022 to generate an accredited test that can be used in clinical trials.
“Early diagnosis of glaucoma can lead to vision-saving treatment, and genetic information can potentially give us an edge in making early diagnoses, and better treatment decisions,” said lead researcher Owen Siggs, PhD, Associate Professor, College of Medicine and Public Health at Flinders University, in a university press release.
Flinders University researchers have been collaborating with scientists at the QIMR Berghofer Medical Research Institute and other research institutes worldwide for some time to identify genetic risk factors for glaucoma, the press release noted.
“In the cross-sectional study of monogenic and polygenic variants related to the disease, the new genetic test was evaluated in 2,507 glaucoma patients in Australia and 411,337 people with or without glaucoma in the UK. The test, conducted using a blood or saliva sample, could potentially detect individuals at increased risk before irreversible vision loss happens,” Medical Device Network reported.
“Genetic testing is not currently a routine part of glaucoma diagnosis and care, but this test has the potential to change that,” said Jamie Craig, PhD, (above), Distinguished Professor, College of Medicine and Health at Flinders University in Australia and senior author of the study, in a press release. “We’re now in a strong position to start testing this in clinical trials,” he added. This is yet another example of how new research is identifying a novel biomarker that could be incorporated into a clinical laboratory test. (Photo copyright: Flinders University.)
Who Is at Risk for Glaucoma?
Glaucoma is a group of eye diseases that are typically caused by a buildup of pressure within the eye. The eyeball contains and produces a fluid called aqueous humour which provides nutrition to the eye and keeps the eye in a proper pressurized state. Any excess of this fluid should be automatically released via a drainage canal called the trabecular meshwork.
But that’s not always the case. When the fluid cannot drain properly, intraocular pressure is created. Most forms of glaucoma are characterized by this pressure, which can damage the optic nerve and eventually cause vision loss and even blindness. Treatments for the disease include medications, laser treatments, and surgery.
Anyone can develop glaucoma, but according to the Mayo Clinic, individuals at higher risk of the disease include:
Individuals over the age of 60.
Those with a family history of glaucoma.
People of African, Asian, or Hispanic descent.
Patients with certain medical conditions, such as diabetes, heart disease, high blood pressure, and sickle cell anemia.
Those with corneas that are thin in the center.
Individuals who have had a past eye injury or certain types of eye surgery.
People who have taken corticosteroid medications, especially eyedrops, for an extended period of time.
Glaucoma is the second leading cause of blindness worldwide, particularly among the elderly. When diagnosed early, the condition is manageable, but even with treatment, about 15% of glaucoma patients become blind in at least one eye within 20 years.
According to the federal Centers for Disease Control and Prevention (CDC), approximately three million Americans are living with glaucoma. The disease often has no early symptoms, which is why it is estimated that about 50% of individuals who have glaucoma do not realize they have the illness.
Thus, a clinically-viable genetic test that is 15 times more likely to identify people at risk for developing glaucoma in its early stages would be a boon for ophthalmology practices worldwide and could save thousands from going blind.
More research and clinical trials are needed before the Flinders University genetic test for glaucoma becomes available. But the discovery alone demonstrates the importance of continuing research into identifying novel biomarkers that could be incorporated into useful clinical laboratory diagnostic tests.
Last-minute court injunction stopped a mass walkout, but allied health workers continue to push country’s District Health Boards for improvements
In New Zealand, the unprecedented surge in PCR COVID-19 testing due to the SARS-CoV-2 Omicron variant appears to have pushed the country’s 10,000 healthcare workers—including 4,000 medical laboratory scientists and technicians—to the breaking point.
On March 3, just 24 hours before the first of two walkouts was scheduled to begin, New Zealand’s Employment Court banned the strike that would have shut down medical laboratories in the country’s mixed public-private healthcare system. Medical laboratory workers make up 40% of the nation’s 10,000 healthcare workers who planned the nationwide strike to protest low pay and poor working conditions, according to 1News.
New Zealand’s Public Service Association (PSA) is the country’s largest trade union representing more than 80,000 workers across government, state-owned enterprises, local councils, health boards, and community groups.
The PSA’s 10,000 health workers (which includes 4,000 medical laboratory workers) had planned to strike on March 4-5 and March 18-19, but, according to the New Zealand Herald the Employment Court stopped the walkouts due to the rise in COVID-19-related hospitalizations.
The Herald noted, however, that PSA union members in Auckland had already postponed their walkout after county District Health Boards (DHB) expressed concern over patient safety.
“Striking has always been our last resort, and our members in Auckland continue to demonstrate their commitment to providing quality healthcare to New Zealanders by working tomorrow,” PSA Organizer Will Matthews told the Herald.
He insisted, however, that DHBs need to respond to workers’ concerns. “The depth of feeling from our members, and the support for industrial action nationwide is unprecedented,” Matthews told 1News. “We are now in a position where strike action is our only remaining option to get the DHBs and the government to listen.”
In an interview with Stuff, medical laboratory scientist Terry Taylor (above), president of the New Zealand Institute of Medical Laboratory Science, acknowledged laboratory workers’ commitment to doing the work, but he is concerned about the next big testing surge. “Goodwill only goes a certain distance in the end when people are knackered and not getting what they need. At the moment, we have the capability to do 50,000 to 60,000 [tests] per day throughout the whole country, but we couldn’t run that for more than a week. We’d be dead, we’d be overrun,” he said. Clinical laboratory leaders in this country may want to make note of Taylor’s concerns, as laboratory conditions in this country become stressed as well. (Photo copyright: Newshub.)
While no new strike dates have been set, Matthews said striking workers would include contact tracers and laboratory staff as well as nearly 70 other groups of healthcare workers, many of whom “don’t even earn a living wage.” According to Peoples Dispatch, allied health workers are working under the terms of a contract that expired in 2020.
The starting salary for a DHB medical laboratory scientist after completing a four-year degree is NZ$56,773 (US$39,519), while lab assistants and technicians start out at less than NZ$50,000 (US$34,804), Stuff reported.
In an interview with 1News, Taylor maintained that diagnostic labs in New Zealand have long been understaffed, undervalued, and their workers poorly treated. The COVID-19 pandemic, he says, has exacerbated an ongoing problem. Issues such as space constraints, for example, have become even more problematic.
“We’ve got extra machinery that’s come into the labs, we don’t get any more space, all these consumables sitting all over hallways and corridors, extra staff coming in to do the stuff,” Taylor told RNZ. “So, we’ve lost all our tearooms, we’ve lost all our office space, our conditions are markedly less than they should be.”
1News points out that the country’s medical laboratory scientists and technicians are processing more than 20,000 PCR COVID-19 tests per day in addition to running 120,000 other samples and 200,000 diagnostic tests. At the end of March 2020, the average number of COVID-19 tests processed per day was 1,777.
While New Zealand has preached to its citizens the need for widespread PCR testing, Taylor argued in February 2022 that the country must change its approach to offering PCR testing only to symptomatic individuals and close contacts.
“To run our diagnostic laboratories into the ground with endless irrelevant testing is a direct reflection of poor foresight, planning, and respect for the role of this critical health workforce,” Taylor told Newshub.
Necessity of Rewarding All Medical Laboratory Personnel
Medical laboratory scientist Bryan Raill is president of Apex, a specialist union of allied, scientific and technical employees. Raill told 1News the long-term solution is for the government to address pay equity, staffing levels, and worker wellbeing in the country’s historically undervalued medical laboratories.
“Medical laboratory scientists and technicians have to be fairly rewarded for the training, skill, and expertise they bring to the health system,” Raill said. “Medical laboratory scientists need a timely, fair, and equitable process to determine their worth.”
While the stresses on New Zealand medical laboratory workers are not identical, US clinical laboratory leaders will want to monitor the lengths to which New Zealand’s laboratory workers are willing to go to force improvements in their working conditions, staffing, and pay.
As the noted above, the government-funded health system is continually strapped for funds. Consequently, the health districts often defer capital investment in hospitals and medical laboratories. That is one reason why lab staff can find themselves working in space that is inadequate for the volume of specimens which need to be tested daily.
Many of the mutations were found at sites on the spike protein where antibodies bind, which may explain why the Omicron variant is more infectious than previous variants
Scientists at the University of Missouri (UM) now have a better understanding of why the SARS-CoV-2 Omicron variant is more infectious than previous variants and that knowledge may lead to improved antivirals and clinical laboratory tests for COVID-19.
As the Omicron variant of the coronavirus spread across the globe, scientists noted it appeared to be more contagious than previous variants and seemed resistant to the existing vaccines. As time went by it also appeared to increase risk for reinfection.
The UM researchers wanted to know why. They began by examining the Omicron variant’s mutation distribution, its evolutionary relationship to previous COVID-19 variants, and the structural impact of its mutations on antibody binding. They then analyzed protein sequences of Omicron variant samples collected from around the world.
“We know that viruses evolve over time and acquire mutations, so when we first heard of the new Omicron variant, we wanted to identify the mutations specific to this variant,” said Kamlendra Singh, PhD, Associate Research Professor, Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine (CVM), in a UM press release.
Kamlendra Singh, PhD (above), an associate research professor in the Department of Veterinary Pathobiology at UM’s College of Veterinary Medicine, led the team that identified 46 mutations of the SARS-CoV-2 Omicron variant. “I went to India last April and I got infected by the Delta variant. So, it then became personal to me,” he told NBC affiliate KOMU. The UM team hopes their findings lead to improvements in existing COVID-19 antivirals and clinical laboratory tests. (Photo copyright: University of Missouri.)
In their paper, the UM team wrote, “Here we present the analyses of mutation distribution, the evolutionary relationship of Omicron with previous variants, and probable structural impact of mutations on antibody binding. … The structural analyses showed that several mutations are localized to the region of the S protein [coronavirus spike protein] that is the major target of antibodies, suggesting that the mutations in the Omicron variant may affect the binding affinities of antibodies to the S protein.”
There are a total of 46 highly prevalent mutations throughout the Omicron variant.
Twenty-three of the 46 mutations belong to the S protein (more than any previous variant).
Twenty-three of 46 is a markedly higher number of S protein mutations than reported for any SARS-CoV-2 variant.
A significant number of Omicron mutations are at the antibody binding surface of the S protein.
“Mutation is change in the genome that results in a different type of protein,” Singh told NBC affiliate KOMU. “Once you have different kinds of protein after the virus and the virus attacks the cell, our antibodies do not recognize that, because it has already been mutated.”
Omicron Mutations Interfere with Antibody Binding
Of the 46 Omicron variant mutations discovered by the UM researchers, some were found in areas of the coronavirus’ spike protein where antibodies normally bind to prevent infection or reinfection.
“The purpose of antibodies is to recognize the virus and stop the binding, which prevents infection,” Singh explained. “However, we found many of the mutations in the Omicron variant are located right where the antibodies are supposed to bind, so we are showing how the virus continues to evolve in a way that it can potentially escape or evade the existing antibodies, and therefore continue to infect so many people.”
These findings explain how the Omicron variant bypasses pre-existing antibodies in a person’s blood to cause initial infection as well as reinfection.
The UM team hopes their research will help other scientists better understand how the SARS-CoV-2 coronavirus has evolved and lead to future clinical laboratory antiviral treatments.
“The first step toward solving a problem is getting a better understanding of the specific problem in the first place,” Singh said. “It feels good to be contributing to research that is helping out with the pandemic situation, which has obviously been affecting people all over the world.”
Singh and his team have developed a supplement called CoroQuil-Zn designed to reduce a patient’s viral load after being infected with the SARS-CoV-2 coronavirus. The drug is currently being used in parts of India and is awaiting approval from the US Food and Drug Administration (FDA).
New discoveries about SARS-CoV-2 and its variants continue to further understanding of the coronavirus. Research such as that performed at the University of Missouri may lead to new clinical laboratory tests, more effective treatments, and improved vaccines that could save thousands of lives worldwide.
