Woman being evaluated at an Ebola clinic in Sierra Leone (Rebecca Rollins, Partners In Health)
26 June 2015. A commercial point-of-care test detecting Ebola virus in the blood of a patient was shown in a field test in Sierra Leone to be as accurate as tests sent to remote labs for analysis. Results of the study led by Nira Pollock of Harvard Medical School and Boston Children’s Hospital were published yesterday in the journal The Lancet (registration required).
While the number of Ebola cases in the West African countries of Guinea, Liberia, and Sierra Leone are considerably fewer than the height of the current outbreak in Fall 2014, World Health Organization says that 20 to 27 new cases are reported each week since the end of May 2015. Clinicians diagnosing people for Ebola, however, are still hampered by the amount time needed to confirm an individual has the virus.
Current test procedures require taking a vial of blood from the individual and sending it, under strict protective procedures, to a lab for analysis. The analysis looks for RNA in the sample with a genetic technique known as reverse transcription-polymerase chain reaction, or RT-PCR, and in many cases requires days to return results before patients can receive care and possibly infecting others.
Pollock and colleagues — from Harvard, Boston Children’s Hospital, and the advocacy group Partners in Health — tested an alternative method made by diagnostics company Corgenix Inc. in Broomfield, Colorado. The Corgenix test uses a self-contained device similar to a home-pregnancy test, and takes a smaller sample of blood from a fingerstick. The device tests the blood sample for a specific antigen protein, VP40, encoded by Ebola viruses, which indicates the presence of Ebola in the patient’s blood, typically in 15 to 25 minutes. Corgenix provided test kits, but were otherwise not involved in the study.
The researchers evaluated the device in February 2015 at two Partners in Health clinics in Sierra Leone, where samples from 106 individuals suspected of having the Ebola virus were analyzed by both the Corgenix point-of-care technique and conventional methods at a Sierra Leone lab. The researchers devised a process for two clinicians to verify the point-of-care readings — made more difficult in some cases by the protective gear — with a third colleague called in if the first two clinicians disagreed.
The findings show all 28 people testing positive for Ebola by the point-of-care technique also returned positive results from the lab analysis. Of the 77 individuals testing negative for Ebola in the lab analysis, 71 or 92 percent also tested negative with the point-of-care technique.
The researchers as well evaluated the Corgenix technique with blood samples collected and analyzed by conventional lab techniques from 284 separate cases throughout Sierra Leone at that time. The separate review returned identical results, where all of the cases testing positive with the point-of-care technique also tested positive using conventional lab methods. Likewise, 92 percent of the samples testing negative through lab methods also tested negative with point-of-care techniques.
The study did point out, however, some limitations in both methods. An analysis using alternative lab methods not available for wide usage found a small number of cases where low levels of Ebola virus went undetected by both the point-of-care and conventional lab tests. Thus, say the researchers, more evaluations of these techniques may be needed to detect Ebola in its earliest stages, particularly in challenging environments.
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Re-Timer light therapy glasses (University at Buffalo)
25 June 2015. Special eyeglasses that adjust circadian rhythms of people with sleep disorders are being tested as a treatment for lung cancer patients with chronic insomnia. The study, led by University at Buffalo (New York) nursing professor Grace Dean, is funded by a $25,000 grant from Oncology Nursing Society.
Insomnia is a common problem among people with cancer, with estimates running as high as 50 to 80 percent for individuals with lung cancer. Dean studies the problem of insomnia in the lung cancer population, which she and colleagues documented earlier this year in a paper published in the journal Cancer Nursing.
The researchers note that cancer patients face challenges such as anxiety from living with cancer and effects of chemotherapy treatments that interrupt sleep. In the paper, the researchers identify some of sleep disorders experienced by lung cancer patients, including difficulty falling and staying asleep — before and during chemotherapy treatment — which they related to an overall lower quality of life.
In the new study, Dean and colleagues plan to test a solution to the problem, a device resembling eyeglasses that shine ultraviolet-free green light into the eyes of wearers, to adjust their circadian rhythms, the physical, mental and behavioral changes that follow a roughly 24-hour cycle. Circadian rhythms respond to light and darkness in the environment.
The device, called the Re-Timer, is made by Australian company Re-Time Pty Ltd. The Re-Timer is designed to help people with insomnia, as well as others with trouble sleeping such as frequent travelers with jet lag and shift workers, gain a more normal sleep pattern. The green light triggers neurotransmitters in the brain encouraging wakefulness, while shutting off other signals encouraging sleep, helping wearers reset their circadian rhythms, and thus better recognize when to be awake and when to sleep.
In their pilot study, Dean and colleagues will ask a sample of people with lung cancer to wear the Re-Timer in the mornings for one hour a day. Participants will wear sensors on their wrists that record amount of sleep and periods of being awake at night. The Re-Timer works with the popular Fitbit activity tracker that monitors sleep as well as exercise.
Dean says a healthy amount of sleep is 7 to 8 hours a night, at 85 percent efficiency, defined as amount of time sleeping, divided by amount of time in bed. She adds that an electronic device like the Re-Timer may be a better solution for people with cancer than sleep medications, which have side effects that could interfere with cancer treatments.
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(Public Domain Pictures, Pixabay)
25 June 2015. An early-stage clinical trial of a drug to treat eye disorders caused by diabetes shows the drug is well-tolerated and reduces swelling in the eye associated with the disease. Stealth BioTherapeutics, developer of the drug brand-named Ocuvia, reported the results today at a company symposium in New York City.
The study is testing Ocuvia among individuals with diabetic macular edema, a complication of diabetes causing blurred vision and vision loss leading to blindness. It occurs when diabetes damages blood vessels in the eye, a condition known as diabetic retinopathy, resulting in leakage of blood and fluid, as well as swelling. Centers for Disease Control and Prevention says diabetes is the leading cause of new cases of blindness among adults aged 20 to 74. Diabetic macular edema is treated today with laser surgery or drugs injected into the eyes.
Stealth BioTherapeutics, in Newton, Massachusetts, develops therapies for disorders related to malfunctioning mitochondria, the energy source in cells. When mitochondria do not function properly, cells have reduced energy and produce excess oxidation, putting increased stress and causing damage to cells and associated byproducts, including nucleic acids and proteins.
Mitochondrial disorders can be inherited or acquired; diabetic macular edema in this case is an acquired mitochondrial disease. The company says Ocuvia, taken as eye drops, acts by protecting against oxidative stress in the eyes caused by diabetes, as well as age-related macular degeneration, a common vision disorder associated with aging.
The clinical trial is testing Ocuvia with 21 people having diabetic macular edema or age-related macular degeneration in Boston; at the symposium, the company reported only on the 15 individuals in the trial with diabetic macular edema. Participants receive either a high dose (1% concentration) or low dose (0.3%) of Ocuvia twice a day in one eye, with the other eye left untreated for comparison, for 28 days.
The trial is looking primarily at the drug’s safety and tolerability, measured by indicators of eye functioning and health, as well as reports of adverse side effects and impact on vital signs. Stealth BioTherapeutics reports that Ocuvia met all of the safety and tolerability objectives in the trial, including “no significant decreases in visual acuity.”
The company also reports that participants have reduced swelling in the eyes receiving Ocuvia, measured by central subfield thickness of the macula — the light-sensitive tissue in the retina that converts light to nerve signals. The central subfield thickness in the treated eyes of participants decreased by 27 to 32 percent, depending on dosage, compared to the untreated eyes that showed no change.
In April, Stealth BioTherapeutics reported that the Food and Drug Administration cleared the company’s plans to expand its tests of Ocuvia to include an inherited form of diabetic eye disease known as Leber’s hereditary optic neuropathy. A clinical trial for this rare disorder is planned in Los Angeles in the second half of 2015.
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(DARPA, Wikimedia Commons)
24 June 2015. The Broad Institute, a molecular medicine research organization affiliated with Harvard University and MIT, and Google Genomics are collaborating to offer a readily-available cloud-based analysis platform for genomic data. Financial aspects of the agreement between Broad Institute — officially Eli and Edythe L. Broad Institute of MIT and Harvard — and Google were not disclosed.
The partnership aims to make genomic analysis easier to access for medical researchers, by offering analytical tools from Broad Institute on a computing platform with sufficient scale and power to process the huge data files produced in genomics. The first step in the collaboration will make available Broad Institute’s Genome Analysis Toolkit on Google’s Cloud Platform.
The Genome Analysis Toolkit is a set of software designed to process different types and collections of genomic data to answer questions from the data for researchers. The specialized software features, called walkers, can be assembled into workflow packages to handle common analytical questions or unique one-off problems. The tools, says Broad, can be applied to genomes from humans as well as other organisms.
The software tools include processing of raw sequencing data for further analysis, as well as discovery, genotyping or characterizing, and filtering of genetic variations from the data. Broad Institute says it logged some 20,000 users of the toolkit, sequencing or genotyping the equivalent of 1.4 million biological samples. Academic and not-for-profit labs can download the software free of charge, while licenses are available to business users.
Google’s Cloud Platform offers cloud-based big data services from hosting and storage of data sets to analytics. The partnership with Broad Institute aims to make it easier for researchers to upload, store, access, and process genomic data, particularly where their own institutions may not have the large-scale infrastructure needed to efficiently run the Genome Analysis Toolkit software.
While hosting the Genome Analysis Toolkit is the first stage in the agreement between Broad Institute and Google Genomics, the parties expect to expand the services over time. In a blog post published today, Google Genomics product manager Jonathan Bingham says “Broad and Google will work together to explore how to build new tools and find new insights to propel biomedical research, using deep bioinformatics expertise, powerful analytics, and massive computing infrastructure.”
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Vision exam with SVOne device (Smart Vision Labs Inc.)
24 June 2015. Smart Vision Labs Inc., a two-year-old company developing vision exam technology that works on smartphones, raised $6.1 million in its first venture funding round. Financing for the New York City enterprise was led by Techstars Ventures, with contributions from Heritage Group, Connectivity Capital, and Red Sea Ventures.
The company’s technology aims to expand the availability of vision exams to people worldwide with uncorrected refractive or focusing errors, but without ready access to optometrists. Smart Vision Labs cites data that even in the U.S. half of the people wearing corrective lenses do not get annual eye exams as recommended by American Optometric Association.
A typical eye exam includes tests for refractive errors that prevent eyes from properly focusing, resulting in nearsightedness, farsightedness, or astigmatism — conditions requiring eyeglasses, contact lenses, or lasik surgery to correct. The tests require individuals to look through a series of lenses where they focus on light from the examiner’s retinoscope, and respond verbally to indicate when the clearest vision is achieved. In some cases automated equipment can determine focusing performance in early stages of the test, followed by refinements with the individuals’ verbal responses.
Smart Vision Labs’ technology is based on wavefront aberrometry that measures the way light travels through the eye, and identifies and measures specific errors in refraction, a technology also employed to identify refractive errors in corrective vision surgery. The company says this technology is superior to conventional eye exams, since it uses objective measurements rather than relying on subjective evaluations and responses from the people being examined.
Smart Vision Labs’ lead product is SVOne, an auto-refractor measurement device attached to an Apple iPhone 5s, designed for handheld use by a clinician. The company says its tests and studies show SVOne measures refraction errors as well as desktop units within 1 percent, and can return results in about 5 seconds per eye. The small size and fast results, says the company, make the device ideal for remote areas and in tests with children.
SVOne is also being tested in the field, particularly in low resource countries where optometrists are scarce. The company is partnering with local entrepreneurial organizations, both for-profit and not-for-profit, on the ground to conduct eye tests in remote villages in Mexico, Haiti, Guatemala, and Dominican Republic. In March 2015, Smart Vision Labs began marketing SVOne in the U.S. after receiving FDA clearance in December 2014.
Yaopeng Zhou and Marc Albanese, founders of Smart Vision Labs, were engineering students at Boston University in 2002, when they worked on a special project with a research institute specializing in vision problems to develop a scanning laser ophthalmoscope to diagnose retinal disorders. In 2013, Zhou and Albanese adopted that experience and founded the company, which soon won a $1 million Powerful Answers Award from Verizon, and secured seed funding from optometry retailer National Vision Inc.
Hat tip: Fortune/Term Sheet
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Red blood cells with sickle cell disease (NCATS.NIH.gov)
23 June 2015. A clinical trial began enrolling participants testing a synthesized therapy for sickle cell disease to improve the flow of blood cells blocked by the condition and relieve the intense pain that results. The late-stage trial is being conducted by drug maker Pfizer Inc., with biotechnology company GlycoMimetics Inc. in Gaithersburg, Maryland.
Sickle cell disease is a genetic blood disorder affecting hemoglobin that delivers oxygen to cells in the body. People with sickle cell disease have hemoglobin molecules that cause blood cells to form into an atypical crescent or sickle shape. That abnormal shape causes the blood cells to break down, lose flexibility, and accumulate in tiny capillaries, leading to anemia and periodic painful episodes, called vaso-occlusive crises. The disease is prevalent worldwide, and affects 70,000 to 80,000 people in the U.S., including about 1 in 500 people of African descent.
In 2011, Pfizer licensed the GlycoMimetics compound code-named GMI-1070, now called Rivipansel. GlycoMimetics discovers and develops synthesized compounds that mimic the structure and activity of carbohydrates, designed to function like traditional drugs, but also to enhance biological functions more than natural carbohydrates. Rivipansel inhibits a broad range of selectins that bind carbohydrates to blood cells and vessel walls and contribute to the blockages characteristic of sickle cell disease. The drug is neither an opioid nor other general pain-reliever.
The clinical trial plans to enroll at least 350 individuals, age 6 and older, with sickle cell disease and hospitalized for a vaso-occlusive crisis. In the study, Rivipansel is being tested against a placebo, looking primarily for the time participants need to be ready for discharge from the hospital. Researchers are also measuring amount of time to actual hospital discharge, total opioid consumption, and amount of time before opioids are discontinued for participants.
Rivipansel received orphan drug designation from the U.S. Food and Drug Administration, and is being reviewed by FDA under fast-track and special protocol assessment programs. Fast-track provides an accelerated review of a new drug application, while special protocol assessment allows FDA to complete its review of a new drug before all late-stage clinical trial results are in.
Under the licensing deal with Pfizer, GlycoMimetics is responsible for early and intermediate-stage clinical trials of Rivipansel, while Pfizer conducts late-stage trials. The agreement allows, however, for a milestone payment of $20 million to GlycoMimetics upon the drug reaching late-stage trials.
Disclosure: The author owns shares in Pfizer.
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Smart insulin skin patch (Zhen Gu Lab, Univ. of North Carolina, Chapel Hill)
23 June 2015. A skin patch made with tiny needles can dispense insulin and regulate blood glucose levels in lab mice for up to 9 hours. The device is being developed by a joint biomedical engineering department at University of North Carolina in Chapel Hill and North Carolina State University in Raleigh, and described in yesterday’s issue of Proceedings of National Academy of Sciences (paid subcription required).
The patch is under development in the labs of biomedical engineering professor Zhen Gu in Raleigh and endocrinologist John Buse in Chapel Hill. Gu, Buse, and colleagues aim to help people with diabetes better control their blood glucose levels with a simple, safe, and inexpensive device. People with diabetes, numbering in the hundreds of millions worldwide and growing, need to measure their blood glucose levels and inject insulin, a process that is often painful and imprecise. In addition, current attempts at closed-loop or self-contained systems use invasive catheters, with mechanical sensors and pumps.
With the patch, the researchers are seeking to emulate the body’s natural system of making, storing, and delivering insulin, where beta cells in the pancreas make insulin, and store it in tiny sacs known as vesicles. When more glucose enters the blood stream, normally functioning beta cells sense the higher levels and respond by making and delivering more insulin.
The team designed the device to also store and dispense insulin with vesicles that form from a reaction of two biocompatible chemicals: hyaluronic acid and 2-nitroimidazole. Hyaluronic acid occurs naturally in the eyes and joints, while 2-nitroimidazole is a natural antibiotic. Combining the two chemicals creates a substance that both seeks and repels water, creating a tiny, nanoscale open space resembling a vesicle. The researchers then fill that space with insulin in solid form and enzymes that react in the presence of glucose.
The patch consists of about 100 of these vesicles in microneedles — which the researchers say pierce the very outer layers of skin, but are too small to cause pain — arrayed on a square sheet about the diameter of a penny. When the enzymes in the vesicles are in the presence of glucose, they oxidize the glucose producing gluconic acid, which consumes oxygen and upsets the equilibrium of the vesicles, causing the vesicles to break open and release insulin into the bloodstream.
The team tested the patch with lab mice induced with type-1 diabetes, the autoimmune disorder affecting about 5 percent of population with diabetes. The mice receiving the patch were able to restore safe blood glucose levels within 30 minutes and lasting up to 9 hours. Mice receiving insulin injections also brought glucose levels under control quickly, but glucose levels also rebounded quickly into dangerously high levels. In addition, the researchers found they could adjust enzyme levels in the patch to keep blood glucose levels within a predetermined range, reducing the risk of receiving too much insulin and driving glucose levels down too far.
The patch still needs more preclinical testing even before clinical trials with humans, but the researchers believe they can design a device that people with diabetes need to change every few days, and customized for each individual’s condition. “The whole system can be personalized to account for a diabetic’s weight and sensitivity to insulin,” says Gu in a university statement, “so we could make the smart patch even smarter.”
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22 June 2015. Current methods of monitoring implanted heart devices, conclude researchers at University of California in San Francisco, may not be adequate for spotting the number of problems with the devices leading to patients’ deaths. The findings of the team led by UCSF cardiologist Zian Tseng were reported today in the journal JAMA Internal Medicine (paid subscription required).
Tseng and colleagues looked into the role of cardiac implantable electronic devices or CIEDs, including pacemakers and implantable cardioverter-defibrillator, in the sudden deaths of individuals with these devices. “With a vast majority of out-of-hospital sudden deaths evaluated by medical examiners or coroners,” says Tseng in a university statement, “CIED problems are often missed in the postmortem investigation, as they are not part of the routine evaluation.”
Implanted heart devices are designed to correct for arrhythmias or irregular heart rhythms, either at a too fast or slow rate or in irregular patterns. Pacemakers control irregular heart rhythms with electrical pulses at the correct beat, to correct for high or low beating rates. An implantable cardioverter defibrillator helps control life-threatening arrhythmias with electric shocks when sensing an abnormal heart beat that can lead to cardiac arrest.
While physicians and manufacturers monitor that performance of heart devices implanted in their patients and customers, the only common system tracking the these devices across the industry is Manufacturer and User Facility Device Experience, or Maude, database maintained by Food and Drug Administration. Participation is mandatory for manufacturers, but voluntary for health care providers.
Health care providers are required to report when implanted heart devices may contribute to someone’s death, but the authors say more than 90 percent of sudden cardiac deaths occur outside hospitals, and autopsies of deaths from these devices are rarely performed. As a result, Tseng and UCSF colleagues collaborated with San Francisco’s medical examiner to perform autopsies on people who died from sudden cardiac deaths, who also had cardiac implantable electronic devices, starting in January 2011 through November 2013.
The autopsies included toxicology and histology tests, as well as device interrogations, looking for any issues with the device, such as hardware failures, algorithm malfunctions, or improper device selection. The results show 22 of the 517 people, or about 4 percent, who had sudden cardiac deaths were fitted with implanted heart devices, with 6 of the 22 dying from other than cardiac reasons.
The researchers found 11 of the 22 deaths — 4 of the people with pacemakers and 7 with ICDs — had device problems, including 3 hardware failures. Other problems included undersensing of irregular heart rhythms, programming errors, and incorrect device selection. A separate review of records for 712 people in San Francisco during the same 3 year period, shows 109 or 15 percent of these individuals died, including 7 with defibrillator issues.
Tseng says issues with cardiac implantable electronic devices need to more systematically tracked and evaluated. “Because these devices are intended to prevent sudden death,” he notes, “careful monitoring for potential device problems should include a complete postmortem investigation when sudden deaths occur in those with CIEDs.”
Disclosure: The author wears a pacemaker.
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Malcolm Whitman and Tracy Keller, left and center, with co-author and radiologist Ralph Mazitschek after 2012 publication on halofuginone (Angela Alberti, Harvard Medical School)
22 June 2015. A joint venture of drug maker Bristol-Myers Squibb and science commercialization company Allied Minds is licensing research at Harvard University on the actions of a Chinese root extract with therapeutic potential against fibrosis, inflammation, and autoimmune disorders. Financial aspects of the agreement between Harvard and Allied-Bristol Life Sciences were not disclosed.
The deal provides Allied-Bristol access to research in the lab of developmental biologist Malcolm Whitman at Harvard’s dentistry school. Whitman and lab colleague Tracy Keller are studying halofuginone, derived from the compound febrifugine found in the roots of a Chinese hydrangea plant known as chang sham. Chinese herbalists, say the researchers, have long used medicines made from febrifugine to treat malaria, fibrosis, and inflammatory diseases.
Whitman, Keller, and associates seek to learn more about the way halofuginone works in the body. Their investigations point to halofuginone blocking a key enzyme that prevents production of certain proteins in the immune system. Those proteins promote the growth of Th17 cells, a type of immune-system T-cell that promotes inflammation, and linked to human autoimmune disorders, where the body’s immune system is tricked into attacking healthy cells and tissue rather than invading disease-causing cells.
A study published in 2012 by Whitman’s lab shows halofuginone blocks Th17 cell activity in lab mice induced with multiple sclerosis. Colleagues on the study at Harvard and affiliated hospitals are already identifying compounds from halofuginone with therapeutic potential for treating fibrosis — growth of excessive scar tissue — and autoimmune diseases.
From the agreement, Allied-Bristol Life Sciences expects to form a subsidiary company to continue drug discovery and development of these and other compounds from halofuginone at least through preclinical stages. Allied-Bristol Life Sciences is a venture of Allied Minds and Bristol-Myers Squibb that finds promising research in academic labs, and forms new enterprises to develop those discoveries from early feasibility stages to preclinical therapy candidates. This subsidiary would be the first spin-off created from the partnership.
Allied Minds, in Boston, acts as a holding company for science and technology-based start-ups in the U.S. The company forms new businesses based on research conducted in the U.S. at university and federally sponsored labs. Allied Minds then provides funding and management for the new enterprises through their initial stages. The company says it has relationships with 33 universities, and 32 labs and research centers affiliated with the U.S. defense and energy departments.
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(Mikael Häggström, Wikimedia Commons)
19 June 2015. A new challenge on InnoCentive asks for biomarkers indicating damage to the liver, conditions that today often require invasive procedures such as biopsies to diagnose. The competition has a total purse of $50,000 and a deadline for proposals of 17 August 2015.
InnoCentive in Waltham, Massachusetts conducts open-innovation, crowdsourcing competitions for corporate and organization sponsors. The sponsor in this case is not identified. Free registration is required to see details of the competition.
The liver is an essential organ in the body for digestion and getting rid of toxic substances. Damage to the liver can occur from genetic causes or result from viruses, heavy drinking, or obesity. Scarring of the liver, known as fibrosis, is an excessive build-up of cell matrix components that interferes with the liver’s functioning, with symptoms occurring such as yellowing of skin and eyes (jaundice), abdominal pain, and swelling of legs and ankles.
Advanced cases of liver scarring can lead to cirrhosis, resulting in permanent damage to the liver, raising the risk of serious complications including liver cancer, and increasing the need for a liver transplant. In addition, infections of the liver, from viruses in blood or sexual contact, can lead to different types of hepatitis that damage the liver.
The sponsor of the challenge is seeking biomarkers — indicators of biological states or conditions — for liver fibrosis. Diagnosing liver disorders today often requires a biopsy, surgical removal of a small piece of the liver for analysis. Biopsies can be painful for individuals with suspected liver disease, thus an important criterion in assessing solutions proposed in the challenge is the degree of invasiveness. Proposed biomarkers should be specific and sensitive indicators that can help guide treatment decisions.
InnoCentive calls this type of competition a theoretical challenge requiring a written proposal that fleshes out an idea before it becomes a proven concept. Proposals submitted in a theoretical challenge usually offer detailed descriptions and specifications showing how the ideas would work.
The challenge has a total purse of $50,000 although InnoCentive does not indicate the number of awards planned or value of individual awards. The sponsor asks competitors receiving awards to grant a non-exclusive license to their intellectual property, after first granting the sponsor a 180-day period of exclusivity to negotiate licensing terms. Entrants not receiving awards will retain all intellectual property rights after the evaluation period.
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