Meet the UNM College of Pharmacy Innovators
Faculty at the College of Pharmacy have dedicated their careers to finding cures, effective treatments and better diagnoses for some of the most deadly diseases. Some of that research, commercialized through the STC.UNM technology transfer organization, has led to U.S. patents on inventions to treat melanoma and tuberculosis and to better diagnose TB, pneumonia and other infections.
Faculty members in the College of Pharmacy have a combined 20 patents affiliated with their work at UNM, with another 34 active patent applications pending.
College of Pharmacy Faculty Turn Science Into Inventions
“Deliver drugs better, that’s my thing,” says Felton, a former practicing pharmacist. “And whatever ‘better’ means. Is it you don’t have to take it as often, so patients will remember to take it? Is it getting better blood levels? Is it getting the drug to the place where it needs to be?”
It’s a vital aspect of pharmaceutical efficacy, because a drug can’t work – or can’t work as effectively – if it isn’t reaching its target at the right strength.
“In particular,” Felton says, “I’m interested in modifying drug release. How quickly does the drug work? What is the dosage? Where is it going to be released? I look at my role as partnering with other faculty who have developed some unique technologies and figuring out how to get it into the body.”
One of her patent applications involves a novel approach to delivering antibiotics directly to an infection.
Felton is looking at loading antibiotics into a porous nanoparticle encased in a lipid bilayer that was developed by the UNM School of Engineering and Sandia National Laboratories. Antibiotics delivered orally or by injection are systemic – they go into the bloodstream and eventually reach their target, the bacteria.
Her invention sequesters the antibiotic in the nanoparticle until it finds the bacteria. “And when it finds the bacteria, it would release the drug right there,” Felton says. “It would lessen exposure systemically and potentially it could be more effective so you would need a lower dose.”
Another of her patent applications, this one for sunscreen, is the opposite of her general quest to get drugs into the body.
Because sunscreens contain small molecules, they penetrate the skin, but it’s only on the skin surface where they are effective. Her question was, can those small molecules be bound to larger molecules so they stayed on the skin surface where they are effective?
“We found, yes, we could keep it on the skin and, even when it was complexed, it was still functioning as a sunscreen,” she says.
Felton also has patent applications for a marker on the inactive ingredients in drugs that could identify legitimately manufactured drugs to help stop drug counterfeiting.
And, she has a patent pending on a formulation of glucosamine and chondroitin, over-the-counter supplements that were found to be effective in treating moderate and severe knee osteoarthritis in a clinical trial conducted through the Department of Veterans Affairs.
Hudson, a professor of pharmaceutical sciences whose interests are in environmental metals and novel therapies for ovarian cancer, collaborated with UNM colleagues Angela Wandinger-Ness, Larry Sklar, Zurab Surviladze, Tudor Oprea, Jeffrey Aubé, Jennifer E. Golden, Chad E. Schroeder, Denise S. Simpson and Julica J. Nöth on a discovery that one component of ketorolac, a nonsteroidal anti-inflammatory (NSAID) approved by the FDA for pain relief, controlled GTPases, the chemical switches inside a cell that regulate biochemical reactions – including cell growth and how cells adhere to each other.
Isolating the R-ketorolac molecule from its S-ketorolac counterpart, Hudson said, “had an activity in cells that was unexpected.”
Their approved patent was for pulling out that component to slow ovarian cancer growth and spread. They are now modifying the application to expand its application to other cancers.
Hudson’s other patent application, with the College of Pharmacy’s associate dean for research, Jim Liu, and others, also looks to repurpose an existing drug in the fight against cancer.
In looking at arsenic, one of Liu and Hudson’s interests, they knew that it inhibits DNA’s ability to repair itself, which often leads to cancer growth.
While they study arsenic as a cancer-causer, Hudson says, “We turned that on its head.
“Our idea, and the basis of the patent, is that if arsenic inhibits DNA repair, then it might increase the amount of DNA damage caused by cancer therapies in the cancer cells,” she says. This increased DNA damage could then lead to greater cancer cell death.
Their idea was that arsenic trioxide, an anti-cancer chemotherapy drug used to treat certain kinds of leukemia, might be used more broadly, in conjunction with radiation and chemotherapy drugs, to boost the efficacy of those treatments by damaging DNA.
While some drug patents recognize new inventions, “utility” patents like these take an existing drug and match it with a new purpose.
“The value of taking these existing drugs to improve cancer therapies is that the time from the idea to human application is much shorter than it is with a new drug,” Hudson says.
McConville, an associate professor of pharmaceutics in the College of Pharmacy for the past three years, specializes in drug delivery and his mind is always on alert for a better way to get the right amount of the right drug to the right place in a patient's body. Recently, he's been concentrating on the part the patient plays in that equation.
Say a patient needs to take an antibiotic three times daily, or a blood pressure drug every morning. "I've been working on a reminder system," says McConville, "because it's very easy to forget."
He pulls out the blister pack, which has been retrofitted with electrical circuits for each pill compartment and a computer chip and small wireless transmitter. If the pill isn't removed and the circuit broken at the right time, it communicates with the chip and by wifi sends a reminder to a cell phone.
If the patient who failed to take the medication ignores or misses the reminder, the phone pings again. And again.
"Repeatedly," McConville says. "And that's the key. You might ignore a reminder once or mean to get to it and then get distracted by other things. If there's something nagging you, you're going to respond."
His wireless medication monitor, which has a patent application pending, continues to remind the patient or caregiver or medical team member until that pill has been removed and its circuit broken.
Another of McConville's innovations is a new way to deliver insulin to diabetics. His polymer strip would hold a prescribed dose of insulin and be placed inside the cheek to be absorbed through the highly vascularized buccal, or cheek wall.
His third area of research involves developing a way to effectively deliver Coenzyme Q10, an anti-cancer agent, to the lung in treatment of lung cancers.
Coenzyme Q10 is a compound that doesn't like water, which has required high doses to effectively dissolve in the body and reach the deep lung. McConville's technique is to process the Q10 so it is 'happier' in water and able cross the cellular membrane.
Another of his innovations, which is close to reaching clinical study, is a coating for intubation tubes to help prevent the common problem of inflammation when they're removed.
"How do I come up with these things?" McConville muses. "I guess I see a problem and then think 'How can we get around it?'"
That the two maps look eerily the same tells Muttil that there are big problems with the current TB vaccine.
"The only TB vaccine, which we have used since 1921, does not work well," Muttil says. "But we still use it because we don't have an alternate."
The work directed by Muttil in his College of Pharmacy laboratory doesn't involve a different TB vaccine — just a way to make the currently used one more effective.
With a $100,000 Gates Foundation grant in 2012, Muttil began to work on two questions.
The first: "I wanted to test a vaccine that would be delivered through the inhaled route," he says. "My thought is TB is a disease that is inhaled into the lungs; why don't we give a vaccine that mimics a natural infection?"
The second: What could be done to prevent the vaccine, which requires refrigeration, from going bad as it travels from first-world factories to third-world vaccination clinics, often by bicycle or camel in stifling temperatures?
The work to answer the first question has been completed and is submitted for publication. In studies involving mice, Muttil's inhaled vaccine was more effective than an injected vaccine. Part of the ineffectiveness of the current injected vaccine is that it is somehow compromised by the environmental mycobacteria that occur in the natural world and enter our body probably via drinking water. In Muttil's study, he found, "If you get the vaccine inhaled, the environmental mycobacteria's effect gets negated. The route of delivery makes a big, big difference."
In addition to being more effective an inhaled vaccine will cut down on the accidental needle sticks and reuse of needles that contribute to the spread of many deadly diseases including Hepatitis B and C and HIV and that it will help with vaccine compliance. Even Muttil, who studies vaccines, suffers from a fear of needles.
The other big hurdle to making vaccines - and not just the vaccine for TB — more effective is to eliminate the need for refrigeration.
Muttil has technology under patent review that would make vaccines stable at high temperatures, and several companies have signaled an interest in investing. A vaccine can be rendered ineffective if it is kept outside the 2 - 8 degrees Celsius range and also if it freezes. It's a narrow window that is hard to guarantee, especially in developing nations in Africa and Asia where vaccine supplies may be shipped in refrigerated trucks or cargo planes to storage facilities and then sent out to more remote areas in coolers, on foot, by bicycle, even by camel.
"As soon as any vaccine hits these peripheral levels of the supply chain, we fail miserably with the cold chain," Muttil says. A study by World Health Organization revealed that almost 50 percent of vaccines given in poor countries go bad before they are used. That means that people who believe they are being protected from disease actually aren't.
With a Department of Defense funding for developing a heat-tolerant vaccine, Muttil has developed powdered vaccines that can stay unrefrigerated for up to a year and a half, or that can withstand exposure to blistering tropical temperatures for many months. His collaborators are currently testing these vaccines in animal studies for their effectiveness.
Muttil, a native of India who saw breaches in the cold chain firsthand, talks about his work in an excited rush.
"I'm always excited," he says. "Because I think there's a lot of potential here. No matter how good the vaccine is, if it goes bad when taken to the real world it isn't making much difference."
Norenberg’s invention is a unique molecule that is selective for lymphocyte function-associated antigen-1, also known as LFA-1, a protein that is expressed on the surface of white blood cells and not by any other normal tissues.
“It’s only on the surface of white blood cells and that makes it a very unique target for imaging,” Norenberg says. “We think that it has some novel applications in imaging infections and inflammations, things like arthritis or lupus. And also it could be important for evaluation the inflammatory component in other diseases.”
For example, some atherosclerotic lesions are benign, but others can break up and form deadly clots. There’s evidence to suggest that the propensity for forming clots is related to the immune cell activity in those plaques. Could this probe give good diagnostic information about which plaques might cause trouble?
Norenberg hopes his approach might also help to better diagnose appendicitis and eliminate some costly and potentially dangerous unnecessary surgeries.
“Right now, appendicitis is a surgical diagnosis,” Norenberg explains. “A surgeon does a rectal exam, palpates the abdomen, says, ‘Well, we think there’s an inflamed appendix. We’re going to go take it out.’ And there’s many billions of dollars spent on unnecessary appendectomies in this country. They go in, they take it out and there’s nothing wrong with it.”
It’s sometimes a waste of money, and it also can cause unnecessary harm to patients, especially the elderly.
“This could provide much more diagnostic certainty,” Norenberg says. “We would inject the patient with the radiopharmaceutical and the appendix would have a lot of immune cells accumulated there and we would be able to image that there is an abnormal accumulation of white blood cells that we think is consistent with appendicitis.”
It’s an example of how investigation in College of Pharmacy laboratories can lead to better patient outcomes in the real world.
“The patents that I have are unique to UNM,” Norenberg says. “No other drug company or academic institution in the world is imaging the same target that we are. There are no other drugs that have ever been developed that work in the same way that this drug works. We hope that we can make a difference in diagnosing diseases earlier and improving outcomes of patients that are being treated for disease where LFA-1 expression is important.”
Todd Thompson pulls a framed document off his bookshelf: United States Patent No. 8,835,506 B2 “Methods and Related Compositions for the Treatment of Cancer”.
It is a patent for using a common antidepressant in the treatment of melanoma that he developed with his wife and fellow faculty member Debra MacKenzie, along with UNM colleagues Tudor Oprea, Larry Sklar, Bruce Edwards and Mark Haynes.
Thompson, who completed his doctoral and postdoctoral studies at the University of Wisconsin after receiving his BS in pharmacy from UNM, also has three patents affiliated with UW.
The core of Thompson’s scientific inquiry is applied science. “I work in line with taking scientific ideas and trying to translate them to make sure that they can help people,” he says. And in the current drug marketplace, patenting an invention is the path to attracting the capital that leads to drug development and puts therapies on pharmacy shelves.
“I think it’s part and parcel of the process,” Thompson says. A patent affords the necessary investment security that allows a company to potentially make money on a drug, so they are willing to invest in bringing it to market.
“I have no interest in doing research if it isn’t going to help people,” he says. “And a drug isn’t going to help people if somebody isn’t going to market it, making therapy available so it can make a difference.”
As a pharmaceutical scientist specializing in molecular toxicology as it relates to carcinogenesis, he says, “My interest in cancer is asking the question, ‘What in the environment can cause a person’s cells to change for cancer to develop? And, if a chemical causes that change, what can you do to modify that change?’
“If I could discover a cure for cancer, that would be my goal,” he says. “My patents, that’s what they’re about – a part of the process in discovering a cure for cancer.”
At Wisconsin, Thompson concentrated on prostate cancer, the most common cancer among men in the United States.
He teased out pentamethylchromanol, a potent antiandrogen, from the Vitamin E molecule, hypothesizing that a molecule that attacked the androgen receptor might work to prevent prostate cancer. Instead, he found that it could kill prostate cancer cells.
His three patents from his work there all involve using pentamethylchromanol in the treatment of prostate cancer.
The drug was tested in animals for toxicity by the National Cancer Institute and is now in clinical trials.
At UNM, Thompson continues to work on prostate cancer therapies, but has broadened his research to other cancers and in doing so patented a treatment for melanoma.
Working with a team from UNM’s Center for Molecular Discovery, Thompson received a National Institutes of Health grant to use a biochemical assay he had developed to screen drugs that were off patent for their original purpose for possible effectiveness on prostate cancer.
His team screened 1,200 drugs and found 80 that looked as though they might be effective. Thompson then asked medical oncologists at the UNM Cancer Center to review those 80 drugs and narrow them down to ones they believed might be most useful against cancer.
Thompson ran those molecules through many different cancer lines and got a surprise.
“All of these drugs were good against prostate cancer, but they were very good against melanoma,” he says. “And there were a couple of drugs that showed extremely potent activity.”
The best was the tricyclic antidepressant nortriptyline.
The patent is for the treatment of melanoma using nortriptyline and Thompson predicts it will become a drug used as part of a combination therapy to treat melanoma.
“What I kind of do is put unusual things together,” says Graham Timmins, an associate professor in the College of Pharmacy’s Department of Pharmaceutical Sciences.
It’s a modest statement from a researcher who holds seven UNM-affiliated patents that involve innovative technology to quickly diagnose tuberculosis and other lung infections. Another of his patents involves a more effective treatment for TB, while another involves evaluating sunscreens for their protection against all potentially damaging solar radiation.
His research is focused on using stable isotope-related compounds and free radical biology – the unusual things he puts together – to better diagnose and treat some common and deadly diseases.
When asked which of those patents he is most proud of, Timmins groans. “Ahh,” he says. “It’s like which of your children do you love the most?”
Let’s start with his rapid breath-test technology, known as the urease breath test. Ureases are bacterial enzymes that are expressed by many bacteria. “If you look at serious lung pathogens,” Timmins says, “most of them have it.”
Timmins’ stable isotope-labeled tracer compound, inhaled by a patient through a nebulizer or inhaler, surveys the entire lung and detects and identifies different infections upon exhalation – and does it within minutes.
“You can screen for tuberculosis,” Timmins says. “You can see if somebody’s got pneumonia. You might be able to see the difference between viral and bacterial pneumonia.”
His rapid breath-test technology patents have led to the creation of a company, Avisa Pharma, headquartered in Santa Fe. The company has raised $8 million and its first clinical development is focusing on using Timmins’s rapid breath test for TB with plans to expand research into pneumonia and cystic fibrosis.
If there is a theme to Timmins’ work, it is speed.
“What we’re trying to do is have a very, very rapid screening test for TB so the whole thing could be over in five or 10 minutes,” Timmins says. The fastest TB diagnostic test now takes three hours and the technology it uses is not very portable. TB, which infects some 9 million people worldwide and results in 1.5 million deaths each year, is most common in developing countries where transportation is limited. It can take a full day for a patient to travel to a clinic or a clinician to travel to an area to test for TB.
“With this,” Timmins says, “you could put everything in a backpack and you could just cycle to a village and test a whole lot of people. If somebody can be diagnosed and have their drug susceptibility determined in that single encounter, then you don’t lose them to follow-up. That’s a major improvement.”
The test has worked in 10 minutes in animal trials.
“Sometimes,” Timmins says, “it’s just speed. You can potentially diagnose earlier in the processes, with the assumption that if you can intervene earlier there’ll be a better outcome.”
Another of his innovations modifies an existing TB drug with stable isotopes to improve its effect on the infection. “It’s very, very complex,” Timmins says. “It’s taken me seven or eight years to figure it out.”
Another patent addresses the efficacy of sunscreens in protecting against melanoma. Sun Protection Factor (SPF) ratings only measure protections against UV radiation, not all of the potentially damaging wavelengths. His patent involves analyzing a sunscreen for all the potential melanoma protection factors.
And another involves using the breath test to diagnose pseudomonas aeruginosa in cystic fibrosis patients. Once it is established, it’s very difficult to eradicate, but when caught early it can be eradicated, so Timmins hopes the test will significantly improve these patients’ lives.
While patents are prestigious and pharmaceutical companies may show profit, Timmins says the questions that underlie the research are his real motivators.
“The reason you do it is to get at these questions,” Timmins says. “Most smart people just like working problems.”