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U.S. Patent Awarded for Freeze-Dried Vaccine Formulation

U.S. Patent and Trademark Office

U.S. Patent and Trademark Office (A. Kotok)

9 September 2014. The technology making possible production and shipping of vaccines in a stable freeze-dried state received U.S. patent protection. Patent no. 8,808,710 was awarded last month by the U.S. Patent and Trademark Office to four inventors and assigned to University of Colorado. Soligenix Inc. in Princeton, New Jersey licensed the technology from University of Colorado in January 2011.

The technology makes it possible for vaccines to be produced in freeze-dried form with aluminum adjuvants, or boosters, and remain potent enough under extremes of heat to generate an immune response. Aluminum salts added to some vaccines, such as diphtheria and tetanus, can improve their ability to produce antibodies. The technology in the patent offers a method for producing and storing vaccines that do not require continuous refrigeration through the supply chain, thus sharply reducing costs and increasing their availability in remote regions.

The patent covers the ingredients in a freeze-dried vaccine formulation and methods in the production cycle such as controlling particle size, selecting aluminum salts for adjuvants, creating a liquid state for the vaccine compound, freezing and freeze-drying the compound, and reconstituting the vaccine into a liquid state. While the patent specifically mentions botulism as a target for the technology, it also claims as part of the composition of vaccines, a wide range of antigens covering potential bioweapons (e.g., anthrax, ricin), influenza viruses, cancer viruses, and many other infectious disease pathogens.

Development of the vaccine technology that Soligenix calls ThermoVax is a joint venture with SRI International, University of Kansas, Tulane National Primate Center, and the New York State Department of Health. The development work is funded by a $9.4 million grant from the National Institute of Allergy and Infectious Diseases, an agency of National Institutes of Health.

Soligenix says ThermoVax is used to produce its engineered ricin vaccine called RiVax and VeloVax to protect against anthrax exposure. The technology is also expected to make it easier for the U.S. Biomedical Advanced Research and Development Authority or BARDA to stockpile vaccines for as part of the nation’s biodefense capabilities. The technology can be applied as well to commercial vaccine production and logistics, where the company cites industry data from 2010 showing 98 percent of all vaccines, valued at $20.6 billion, are shipped using refrigerated transport and storage.

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Advance Achieved in Replacement Kidney Blood Vessels

Anthony Atala

Anthony Atala (WakeHealth.edu)

9 September 2014. Researchers at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina succeeded in keeping open for 4 hours blood vessels in lab-made pig kidneys, a key step in developing replacement kidneys for patients needing transplants. The work is described in an article published last week in the journal Technology (registration required).

The team, led by Anthony Atala, director of Wake Forest’s Institute for Regenerative Medicine, sought a technique for extending the effective blood flow for replacement kidneys, which up to now, was limited to 1 or 2 hours, on devices sized more for rodents than humans. Earlier attempts ran into problems with blood clots forming in the blood vessels to the kidney, making them more of a danger than a therapy to the patient.

The replacement organs start with kidneys from pigs, which are about the same size as human kidneys, but with the natural organ cells removed, leaving the underlying scaffolding matrix, and a network of blood vessels supporting it. That scaffold is then seeded with the patient’s own cells to grow into a new kidney, which would be less likely to encounter organ rejection than a transplanted kidney from another human donor.

Clots forming in the blood vessels supporting the kidney presented a continuing problem, however, that limited progress. The problems occurred in the endothelial cells, those lining the blood vessels. The researchers traced the problems to methods for seeding the vessels with the patient’s own cells, where the replacement cells became detached and encouraged formation of clots.

Atala and colleagues tested several alternative methods for seeding the kidney’s blood vessels with endothelial cells and found a combination of techniques to address the problem. The team started with using a syringe to introduce the cells to the blood vessels, then increased the flow rate of cells as they accumulated along the lining of the blood vessels. They then coated the blood vessel linings with an antibody corresponding to a peptide known as CD31 that helps keep the endothelial cells in place.

The authors implanted and tested the engineered kidneys in pigs weighing 90 to 110 pounds, and found the combination of new seeding technique and antibody kept the replacement blood vessels open for 4 hours, more time than achieved before. “In our proof-of-concept study, the vessels in a human-sized pig kidney remained open during a 4-hour testing period,” says Atala in a Wake Forest statement. “We are now conducting a longer-term study to determine how long flow can be maintained.”

The researchers believe the cell seeding techniques can be applied as well to other engineered replacement organs, such as liver or pancreas.

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Grant Funding Crowdsourced Multiple Sclerosis Drug Trial

White pills in a prescription bottle (Photos8.com)

(Photos8.com)

8 September 2014. A grant from a National Institutes of Health agency is funding a crowdsourced clinical trial of a generic blood pressure drug to help treat multiple sclerosis. The $1.4 million grant from National Center for Advancing Translational Sciences (NCATS) is supporting an intermediate stage clinical study by Transparency Life Sciences LLC, a drug development company in New York using open-innovation techniques.

The grant, issued under the Small Business Innovation Research program tests the blood pressure drug lisinopril as a supplementary treatment for multiple sclerosis. Lisinopril is one of a class of angiotensin-converting enzyme (ACE) inhibitors that reduce chemicals constricting blood vessels, enabling the heart to pump more efficiently. The drug is now available in generic form to treat hypertension, or high blood pressure.

Multiple sclerosis is a disorder where the immune system is tricked into attacking the protective myelin sheath that covers nerve cells. Damage to the myelin interferes with signals between the brain and the rest of the body, causing a wide variety and severity of of symptoms, but can lead to disability. There is no cure for multiple sclerosis and current treatments are designed to help recover from attacks and manage symptoms.

Transparency Life Sciences licensed rights to research by one of its founders, Lawrence Steinman of Stanford University, on the potential for lisinopril to improve the efficacy of multiple sclerosis drugs. Because lisinopril is widely used as a blood pressure treatment, it’s safety profile is well established. The drug’s low cost makes it attractive to NCATS, which is charged with speeding basic biomedical research to the clinic, including the search for new uses for current drugs.

Transparency Life Sciences conducts clinical trials through crowdsourcing techniques that design the studies with specific questions pertaining to the diseases being addressed and the treatments proposed. The crowdsourced responses are collected and synthesized into a protocol for the study. A protocol building exercise for this study is already underway. The company also crowdsources ideas for new applications for current drugs.

The trials also make maximum use of telemedicine to conduct the trial, thus enlarging the potential pool of participants while holding down costs. For this trial, Transparency Life Sciences hired the services of AMC Health, a company providing telemedicine services, including clinical trial monitoring.

The trial will be conducted by Mount Sinai Hospital medical school, led by neurology professor Fred Lublin.

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Synthetic Platelet-Like Particles Developed, Tested

Boxes of Red Cross bllod platelets (Jason Scragz/Flickr)

(Jason Scragz/Flickr)

8 September 2014. Biomedical engineers and medical researchers designed and tested in the lab a new type of synthetic particle that acts like natural blood platelets to help heal bleeding. The team from Georgia Institute of Technology and Emory University medical school, both in Atlanta, published its findings yesterday in the journal Nature Materials (paid subscription required).

Platelets are cells in the blood whose function is to stop bleeding from broken blood vessels. When platelets in the blood are working properly and at normal levels, they respond to signals of a damaged blood vessel from a protein known as thrombin and accumulate at the site forming a clot, which slows the blood flow. The clot forms by platelets depositing a natural polymer called fibrin at the point of damage, which changes the shape of the platelets and lets them clump together in a clot to staunch the blood flow.

The Georgia Tech/Emory team led by biomedical engineers Thomas Barker and Andrew Lyon developed tiny soft synthetic particles from a biocompatible hydrogel material, about 1 micron — 1 millionth of a meter — in diameter. The team designed the particles to respond to a bleeding episode in much the same way as a natural platelet, by accumulating the fibrin polymer at the spot of the blood vessel damage. To respond to the bleeding, the researchers attached to the hydrogel particles an antibody that attracts the fibrin enabling a clot to form.

The team tested the synthetic platelet particles in microfluidics — lab-on-a-chip — devices with channels to simulate blood vessels in a fresh wound, coated with cells found on the inside lining of natural blood vessels. When the synthetic particles were added to human blood low in platelets, the blood formed clots in the simulation devices, much like blood rich in platelets. The researchers report similar results in tests with lab animals.

Barker, Lyon, and colleagues conducted more proof-of-concept lab tests with the synthetic particles. One set of tests was conducted with blood from infants who had open-heart surgery, where their blood is diluted to improve blood flow and reduce clotting. In these tests, the particles helped the diluted infant blood form clots. Further tests with blood from hemophiliacs, who do not have fibrin in their blood to form clots, showed the synthetic particles did not, as predicted, form clots, since there was no fibrin to respond to the antibody attached to the particles.

The authors say the synthetic platelet particles still have more questions to answer, including how the body eliminates the particles, as well as their performance in human clinical trials. The particles were originally developed as a form of first-aid for wounded soldiers, who could even self-administer the particles on the battlefield. The researchers believe the particles could also reduce the need for transfusions for surgery or chemotherapy patients.

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Asthma/COPD Device Maker Lands $14.5M in Venture Funds

Illustration of lungs (Mikael Häggström/Wikimedia Commons)

(Mikael Häggström/Wikimedia Commons)

5 September 2014. Propeller Health in Madison, Wisconsin, developer of a system to track respiratory disorder medications in real time, secured $14.5 million in its second round of venture financing. The funding round was led by venture investment company Safeguard Scientifics, with participation by the Social+Capital Partnership, Propeller Health’s previous funding source.

The Propeller Health system is designed to help people with asthma and chronic obstructive pulmonary disease or COPD track their maintenance therapy. Asthma is chronic condition, where the airways become inflamed and narrow, causing people with asthma to experience wheezing, shortness of breath, tightness in the chest, and coughing for periods of time. Centers for Disease Control and Prevention estimates that in 2010 asthma 18.7 million adults had asthma, along with 7 million children.

COPD has symptoms resembling asthma, including wheezing, shortness of breath, and chest tightness, but COPD is more of a progressive disease where the airways and air sacs in the lungs lose their flexibility, become inflamed, or make more mucus than usual, preventing blood vessels in the lungs to bring in oxygen and remove carbon dioxide. There are two major forms of COPD, emphysema and chronic bronchitis, together affecting at least 15 million people in the U.S., mainly over the age of 65, according to CDC.

People with asthma or COPD are asked to keep close track of their symptoms and events that trigger attacks or exacerbations that cause flare-ups of the symptoms, as well as record use of medications, such as rescue inhalers, to relieve those symptoms. With COPD in particular, exacerbations can make the disease progress faster and result in hospitalization. Keeping a diary, however, is an unreliable record and not easy for many people to maintain.

The Propeller Health system combines a medication sensor that fits over the the inhaler and measures the amount of medication administered with each use. Those data are captured in software on a smartphone app — iOS and Android versions are available — via a Bluetooth connection that adds the location with date and time, to provide an ongoing record of medication use. The software also allows patients to record symptoms. The data are then transmitted to parents and physicians, who can make any adjustments in the medications if warranted by these reports..

The company plans to apply the funding round’s proceeds to product development, new alliances, and marketing. In May 2014, FDA cleared a new version of the system with a smaller sensor to conserve battery life and more sophisticated analytics. In July, Arizona Care Network, an accountable care organization, began offering the Propeller Health system to its members with COPD. Accountable care organizations are groups of health care providers that voluntarily coordinate their services, particularly for patients with chronic diseases.

Safeguard Scientifics, in Wayne, Pennsylvania, is a venture investment company that specializes in growth-stage enterprises working in health or medical technologies developing innovative solutions, with intellectual property protection and a rapid path to commercialization. The company generally makes initial investments of $5 to $15 million.

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Hat tip: Fortune/Term Sheet

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Coffee Genome Sequenced, Caffeine Enzymes Analyzed

Coffee beans

(Harald Hoyer, Wikimedia Commons)

5 September 2014. An international team of researchers sequenced the genome of a major type of coffee that revealed the evolutionary pathway of this popular drink, and more details about caffeine, a main attraction of coffee. The team was led by Institute of Research for Development and National Sequencing Center, both in France, and University at Buffalo in New York. The findings appear in this week’s issue of the journal Science (paid subscription required).

According to International Coffee Organization, coffee is grown in 70 countries, mainly in tropical and sub-tropical regions, producing some 8.7 million metric tons (9.6 million short tons) in 2013. For many of the countries, coffee is an important cash crop and income generator. International Coffee Organization estimates in 2010 coffee production generated $15.4 billion in revenue and employed some 26 million people worldwide.

The research team — from institutions in Europe, Asia, and North and South America — used a whole genome shotgun sequencing strategy that reveals the order of all DNA molecules in an organism. This analysis makes it possible to pinpoint the evolution of the organism and identify similarities or differences in other species. The results offer a better understanding of strengths and weaknesses of the species, which makes possible tweaks in the genome to make coffee, in this case, resist pests or adapt to changing climatic conditions.

The researchers analyzed the genome of Robusta coffee (Coffea canephora) that accounts for about 30 percent of worldwide coffee production, grown in West and Central Africa, as well as Southeast Asia and Brazil. The team compared the sequencing data from Robusta coffee with a similar analysis of tomatoes, grapes, and Arabidopsis, a well-documented reference plant.

The findings show the coffee genome has similarities in evolutionary development to grapes and tomatoes, but coffee evolved separately, creating unique and more stable families of genes, including those that give coffee its recognizable aroma and flavor. These unique gene families also help make Robusta more resistant to disease than Arabica coffee, grown in more regions of the world.

“By looking at which families of genes expanded in the plant,” says Buffalo biologist and senior co-author Victor Albert in a university statement, “and the relationship between the genome structure of coffee and other species, we were able to learn about coffee’s independent pathway in evolution, including — excitingly — the story of caffeine.”

Caffeine not only produces the mild stimulants that attract drinkers, it is also believed to give the plants protection against pests and disease. The analysis revealed that the genes producing enzymes known as N-methyltransferases or NMTs in turn produce the caffeine in coffee. While this process is similar in tea and cacao, which also produce caffeine, the analysis shows the NMT-producing genes in coffee developed separately from tea and cacao.

Albert tells more about the study in the following video.

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PBS to Air Documentary on Vaccine Attitudes and Disease

Paul Offit and Sonya Pemberton

Paul Offit, left, and Sonya Pemberton (A. Kotok)

4 September 2014. Public Broadcasting Service (PBS) will air a documentary next week on the changing public attitudes toward vaccines and their effects on the growing occurrence of communicable diseases in the U.S. The show, Vaccines — Calling the Shots premieres on PBS as part of the NOVA series of science documentaries on Wednesday 10 September.

At a briefing today for media in Washington, D.C., the show’s producer-director and some of the experts appearing in the film described the degree of public resistance to vaccinations for children, which appears to be bringing back more cases of diseases once thought eradicated. Centers for Disease Control and Prevention reports as of the end of August 2014 nearly 600 cases of measles in the U.S., for example, the largest number in 20 years. Also as of August, the state of California declared a pertussis or whooping cough epidemic, with more than 7,500 cases reported so far in the state this year. Refused or delayed vaccinations are considered a prime cause of both outbreaks.

Paul Offit, director of vaccine education at Children’s Hospital in Philadelphia, outlined the idea of community or herd immunity, a situation where nearly all people in a community are vaccinated against a disease, which sharply reduces chances for that disease to spread, and the keeps the disease contained. However, once the rate of vaccination drops below 95 percent, said Offit, herd immunity begins to break down for diseases like measles.

One of the reasons for growing resistance to vaccinations, Offit noted, is the lack of awareness of the suffering these diseases can cause. Before development of the measles vaccine in 1963, measles was familiar and feared, causing 38,000 hospitalizations and 500 deaths a year. Offit told about dealing personally with a measles outbreak in Philadelphia in 1991, causing 1,400 cases and 9 deaths. “The city was in a panic,” he added.

Sonya Pemberton — a film maker, science journalist, and the show’s producer, director, and lead writer — noted the small numbers of people who are adamantly opposed to vaccinating their children, about 1 percent, but still have an influence on many more who have questions about vaccine safety. Pemberton estimates those opposed or questioning vaccinations comprise about 10 percent of the population, a relatively small percentage, but enough to break herd immunity.

Pemberton recommended speaking to parents with questions or concerns about vaccines “respectfully and acknowledging people are not necessarily outright refusing, but are concerned.” People with concerns about vaccines will get all kinds of information over the Internet, and you need to deal with those fears with sensible and impartial information based on science. “It is okay to talk concerns and fear,” said Pemberton, noting that “acknowledging fear helps people deal with fear.”

Brian Zikmund-Fisher, a psychologist and professor of public health at University of Michigan, studies perceptions of risk associated with vaccines. He noted that vaccines are among the safest of medicines made, yet on a personal level, it is often difficult to sell parents — the vast majority of whom never experienced the diseases — of the benefits of a vaccine, as long as there are fears about safety. Zikmund-Fisher said discussing statistical probabilities, no matter how small, does not work, adding “parents care about possibility not probability.”

Joe Lawlor, a health reporter for the Portland Press Herald in Maine, wrote a series about vaccines in Maine that suffered a pertussis outbreak in 2012.He said the series got some 600 comments, about 10 times the usual number.

Maine, like most states, allows parents to opt out of vaccines for religious or philosophical reasons, and nearly 4 percent of parents exempt their children from vaccinations. Some of the resistance is political, Lawlor said, where some people object to government telling parents what to do. Nonetheless, Washington State tightened their exemption requirements, which resulted in fewer disease outbreaks in that state.

In response to a question from Science and Enterprise, Offit said pediatricians do a better job at explaining the rationale behind vaccines for children than family practitioners convincing adults to get vaccinated for the flu or shingles. While family practitioners are doing better, he still called vaccination rates among adults “woeful.”

Zikmund-Fisher added people tend to be more protective of children than themselves. “Children are people that are looked upon as needing special protection,” said Zikmund-Fisher, “and that makes the conversation more difficult when the tradeoff between benefits and risks comes to the surface.”

Vaccines -- Calling the Shots logo

(PBS.org)

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Calico, AbbVie Partner on Aging Disorder Therapies

Hands with arthritis (NIH)

(National Institutes of Health)

3 September 2014. California Life Sciences LLC, better known as Calico, and the pharmaceutical company AbbVie Inc. are collaborating on discovery and commercialization of drugs for age-related diseases such as cancer and neurodegenerative disorders. The partnership, which includes building a new research center, could result in a joint investment as high as $1.5 billion.

Calico, started a year ago by Google, aims to address diseases associated with the aging process and that degrade the quality of life as people age. Google last year recruited Arthur Levinson as the company’s CEO. Levinson was chairman and CEO of the biotechnology company Genentech, now a subsidiary of Roche, and is currently chairman of Apple. Levinson also served on Google’s board from 2004 to 2009.

Under the deal, Calico and AbbVie will each contribute $250 million to fund the partnership, including the building of a research and development center in the San Francisco Bay region. Calico will concentrate on drug discovery and early drug development, through initial intermediate-stage clinical trials.

AbbVie plans focus on later-stage clinical trials and commercialization that advance new drugs to the marketplace. Both companies are expected to share costs and profits. The companies also agreed that further financial contributions could reach as high as $500 million from each party.

AbbVie currently has in its pipeline drugs and biologics for various disorders associated with aging, such as osteoarthritis, Parkinson’s disease, and both blood-related and solid tumor cancers.

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Multi-Purpose Drug Boosts Adherence After Heart Attack

Human heart and arteries (Yale School of Medicine/Wikimedia Commons)

(Yale School of Medicine/Wikimedia Commons)

3 September 2014. Researchers at Mount Sinai Hospital in New York and National Centre for Cardiovascular Research in Madrid, Spain found a pill combining three cardiovascular drugs usually prescribed separately helps heart attack patients stick to their medications better than the three drugs taken separately. The team led by Valentin Fuster, accredited to both institutions, presented its findings yesterday at the European Society of Cardiology meeting in Barcelona.

Physicians treating people who suffer heart attacks often report problems getting their patients to stick to their prescribed medications, with non-adherence rates at 60 percent or more, which impedes the patients’ recoveries. The authors cite data estimating half of the reduction in cardiovascular deaths in Western countries in the past 20 years can be attributed to heart attack patients taking their medications as prescribed, thus improving medication adherence can lead to fewer subsequent heart attacks.

Fuster and colleagues first surveyed the medication adherence behavior of 2,118 people in Spain, Italy, Argentina, Brazil, and Paraguay who suffered a heart attack to establish baselines and uncover reasons for not taking prescribed medications. Their analysis revealed less than half (46%) of heart attack patients in these countries took their medications, with reasons for non-adherence occurring more among younger patients and those with depression, as well as patients citing problems following a complex regimen, poor health insurance, and a low level of social support.

The team then designed a clinical trial to test a drug containing three medications usually prescribed separately, against the usual practice of prescribing the individual drugs. The trial tested the drug Trinomia, made by Ferrer Laboratories, a Spanish pharmaceutical company, containing:

– 100 milligrams (mg) of aspirin that acts as a blood thinner

– 40 mg of simvastatin, a statin drug to control cholesterol levels

– 10 mg of ramipril, an angiotensin-converting enzyme (ACE) inhibitor to treat high blood pressure

The trial recruited 695 patients from four of the countries in the original analysis — Italy, Argentina, Brazil, and Paraguay — who suffered heart attacks, randomly assigned the patients to receive Trinomia or the three separate drugs, and followed their progress for 9 months. The researchers measured adherence through a standard drug-adherence questionnaire and an audit of the drugs maintained by the patients.

The trial results showed more patients taking the single pill stay with medication schedule (63%) than patients taking three separate medications (52%), with the findings consistent for both the questionnaire and the pill counts. The follow-up also revealed, however, no statistically reliable differences between the single or multiple-drug groups in average blood pressure, cholesterol levels, serious adverse effects, or deaths.

A longer-term trial is in development, says Fuster in a Mount Sinai statement, to test if improved drug adherence with the multi-purpose drug leads to reductions in subsequent heart attacks.

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Breakthrough Status Given Parkinson’s Psychosis Drug

Brain networks illustration

(DARPA.mil)

2 September 2014. Acadia Pharmaceuticals says the U.S. Food and Drug Administration designated its drug candidate pimavanserin as a breakthrough therapy for the treatment of psychosis associated with Parkinson’s disease. Acadia is a biopharmaceutical company in San Diego specializing in neurological and central nervous system disorders.

Pimavanserin is Acadia’s lead therapy candidate, to be offered under the trade name Nuplazid, and designed for patients with Parkinson’s disease experiencing periods of psychosis. Parkinson’s disease is probably best known for its physical symptoms like tremors and balance problems, but the disorder can also lead to psychiatric symptoms including hallucinations and delusions.

The company cites data indicating up to 40 percent of Parkinson’s disease patients have occurrences of psychosis, with no treatment yet approved for the condition in the U.S. Patients with psychosis as well as the physical symptoms experience a sharply reduced quality of life and impose a significant burden on caregivers.

Pimavanserin is a small molecule drug that binds to receptor proteins in the brain associated with psychosis, and exert a controlling or moderating influence on those receptors. The drug is administered orally once a day. In October 2013, Acadia reported results of a late-stage clinical trial in the journal The Lancet showing Parkinson’s disease patients taking pimavanserin have fewer experiences of psychosis, such as hallucinations and delusions, while maintaining motor control, compared to a placebo.

FDA designates therapy candidates as breakthroughs when they address a serious condition and demonstrate through clinical evidence that the treatment is a substantial improvement over current methods. Once designated as a breakthrough therapy, a drug or biologic can receive early and frequent communications with FDA staff, quick resolution of questions, intensive guidance on drug development, and an organizational commitment from top managers at FDA.

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