Tech Transfer: Open for Business

Here are some things that David Sullivan knows how to do: He knows how to manage a modestly sized biological lab. He knows how to chemically test for proteins and other molecular markers of Plasmodium, the parasite that causes malaria. He knows how to build simple prototypes of diagnostic devices that can detect Plasmodium proteins in urine—a potentially enormous breakthrough because such devices could eliminate the expense and risk of malarial blood screenings. Those are the kinds of tasks to which Sullivan, MD, an associate professor in Molecular Microbiology and Immunology, has given the last 20 years of his life.

But here are a few things that Sullivan doesn’t know how to do: He doesn’t know how to organize and finance large-scale trials of his malaria diagnostics. He doesn’t know how to secure international patent protection for the devices. And he has no idea how to find factories that might manufacture them on a mass basis.

To fill in those gaps—and to increase the odds that his lab’s ingenuity will actually benefit people on the ground—Sullivan turned to the Johns Hopkins Technology Transfer Office.

In 2008, that office licensed Sullivan’s invention to Fyodor Biotechnologies, a small Baltimore company led by a former researcher from the Johns Hopkins School of Medicine. If all goes according to plan, Fyodor will conduct field trials of the urine diagnostic in Mali this spring. Hopes are running high, because an effective replacement for blood-based tests could have profound benefits in combating the disease that kills nearly 700,000 people annually. “We’ve been using a more than 100-year-old test, jabbing someone with a needle,” Sullivan says. “Our idea is to make malaria diagnostics more accessible to people in the home, almost like a pregnancy test. This may enable faster treatment and faster contact with health care personnel.”

Sullivan’s project is just one of several tech transfer ventures that have emerged from the Bloomberg School in recent years. Those efforts don’t always come easily or naturally to public health scholars. “The culture here has historically not been geared toward tech transfer,” says Shyam Biswal, PhD, a professor in Environmental Health Sciences and one of the founders of Cureveda, a biotech venture that aims to create new therapies for inflammatory diseases. When you’re working on problems that afflict people in severe poverty, revenue streams are probably the last thing on your mind. For their part, tech transfer offices haven’t always known what to do with public health ideas that might not have a market in the U.S. Slowly but surely, however, both parties are learning how to make this marriage work. In certain circumstances, they have realized, the market might be the only way to ensure that a promising public health tool moves from the lab into the real world.

“The tech transfer process can be frustrating because so many good ideas die on the vine,” Sullivan says. He is grateful that Hopkins’ tech transfer staff brokered his lab’s relationship with Fyodor. If the Mali trials go well, the company hopes to have the malaria diagnostics certified by the WHO, opening the door to potential large-scale purchases by The Global Fund.

“In this day and age, if you just publish an idea, it probably won’t get done,” says Wesley D. Blakeslee, director of the Johns Hopkins Office of Technology Transfer. “I think there’s more of a recognition now that biotech companies can be partners with us. If you invent a cure for cancer and it only stays in the lab, doesn’t get out the door, then you haven’t had the impact.”

Sullivan’s malaria diagnostic is just one among a diverse array of tech transfer ventures based at the Bloomberg School. They include a screening instrument for identifying aging adults at highest risk for intensive hospitalization; a set of prospective new therapies for chronic obstructive pulmonary disease; and a series of instructional videos designed to teach doctors how to candidly acknowledge and apologize for medical errors.

Then there is the grandfather of Bloomberg School tech transfer efforts, which also happens to be the most lucrative in Johns Hopkins University history: the Adjusted Clinical Groups (ACG) System. The software package allows public health agencies, insurers and scholars to analyze and predict patterns of illness across large populations. More than two-thirds of gross royalties from ACG (which was first made commercially available in 1992) have been poured back into the Bloomberg School’s research programs.

The tech transfer process begins when a scholar files a formal disclosure of invention to the University. If the idea seems at all promising, the University then files a provisional U.S. patent application—a relatively low-cost step that posts a claim on the concept for a 12-month period. Then the waiting game commences: If a company chooses to license the invention, that company usually assumes responsibility for pursuing permanent patent protection—a process that can involve hundreds of thousands of dollars in legal fees. But if no suitor emerges during the 12-month period, then the tech transfer office needs to decide whether to roll the dice and invest the University’s own money in permanent patent filings.

That was the dilemma that Sullivan’s urine-based malaria diagnostic faced in early 2006, 12 months after his preliminary patent application had been filed. In his case, the University decided to press forward with a permanent application, and the gamble paid off. Two years later, in 2008, Fyodor Biotechnologies licensed the technology—and agreed, as is typical in such cases, to reimburse the University for the money it had spent on patent fees.

“I’m hoping that we get the big blockbuster, for all the benefits that it would bring to our institution. We’ve come close a few times.” —Wesley D. Blakeslee

That basic pattern is common, according to Blakeslee. Roughly 70 percent of the licenses that Hopkins signs are for inventions that had been developed at least three years earlier. In 2010, Hopkins spent more than $8 million on patent filings (that figure includes the staff time of the tech transfer office’s in-house attorneys), and received $3.79 million in patent fee reimbursements from licensees.

“We push our inventions continuously,” Blakeslee says. “Today the biggest part of our job is to engage with industry to find out their needs, and when we do, we examine our entire portfolio for a fit.”

But even if a three-year wait is typical, it was still disheartening for Sullivan, who says he has seen many good public health ideas founder because they don’t fit the profit-making imperatives of the pharmaceutical industry. “Timing is everything,” he says. “If a company is not ready to pick it up, then the idea just sits there.” He says that the Hopkins tech transfer office seems to be stronger than many of its counterparts at other universities at breathing life into ideas aimed at the developing world.

Blakeslee happily concedes he daydreams about lucrative pharmaceuticals with Western markets. “I’m hoping that we get the big blockbuster, for all the benefits that it would bring to our institution,” he says. “We’ve come close a few times.” But he says his office also uses a variety of strategies to support low-profit-margin ideas like Sullivan’s. Last year, his office brought together more than 80 scholars from across Hopkins at a meeting with representatives of GlaxoSmithKline’s “Open Lab” project, a nonprofit effort to develop new drugs to treat tuberculosis and other diseases of the developing world. The University has also made a low-cost licensing deal with the PATH Malaria Vaccine Initiative for a technology that was developed at the Bloomberg School.

One way for public health scholars to cope with economic constraints is to be more strategic about their research programs, according to Douglass B. Given, a biotechnology investor who serves on the Bloomberg School’s Health Advisory Board. Given believes that scholars at Hopkins and elsewhere should be more aggressive about finding venture capitalists and philanthropic partners to support the commercialization of new treatments for neglected diseases.

The key, Given says, is to spot emerging waves of research financing—say, a new international anti-tuberculosis campaign, or surging interest in particular kinds of recombinant gene technology—and to concentrate an entire academic department’s resources on those themes. “You need to think about where the government funding is and where the school’s strengths lie,” says Given. “If you don’t use those kinds of strategies and screens when you hire faculty members, then you can wind up in a funding no-man’s-land.”

Biswal, the inflammatory disease researcher, says that the tech transfer climate at Johns Hopkins has “radically improved” since he first dipped his toes in the water seven years ago, but he believes much more can be done. One element that he does praise is the Bloomberg School’s program of seed grants for new tech transfer ventures. The School now awards up to three $50,000 grants each year for scholars who want to develop a business plan or to file patent applications. Biswal has won two of those grants, and he says that his Cureveda venture would have been impossible without that initial support. The grants allowed him and his colleagues to develop an infrastructure and to hire a chief executive officer, he says—and it was only after that foundation was in place that larger pharmaceutical companies began to knock on his door. (Cureveda now has a three-year research and development contract with GlaxoSmithKline.)

In the rare cases when university inventions lead to lucrative products and services, they can generate substantial streams of revenue. Under the terms of the Bayh-Dole Act of 1980, the federal law that established the modern day template for commercializing academic research, universities must reinvest their licensing payments and royalties in their research programs. At Johns Hopkins, those revenues are generally allocated as follows: 35 percent to the inventor, 15 percent to the inventor’s laboratory, 15 percent to the inventor’s department, 30 percent to the inventor’s school and 5 percent to the University as a whole.

ACG, for example, has brought revenue to the Department of Health Policy and Management—where one of its primary creators, Jonathan P. Weiner, DrPH ’81, MS, is based—and to the School. Most of this revenue comes from insurance companies and public health systems in more than a dozen nations—including the Medicaid programs of 15 U.S. states and systems in Canada, Spain, Taiwan and the United Kingdom—that use ACG’s software to analyze patterns of health care delivery and costs. But Weiner emphasizes that the system is also available to academic researchers at low or no cost. “We’ve developed a huge research and development program out of this,” he says. “It’s not just about industry.”

Weiner believes he and his colleagues struck the optimal balance: They kept the ACG venture under the Hopkins roof rather than simply selling it to an external company. “Sometimes academics start a company or sell their patent,” he says, “but then that company is gobbled up seven times over and the project all but disappears.” By keeping ACG in-house, Weiner says, his team has been able to maintain the concept’s quality through nine or 10 iterations.

Quality control has also became crucial to Charles E. Boult, MD, MPH, MBA, a professor of Health Policy and Management, who helped to develop Guided Care, a health care delivery model aimed at improving services for older adults with multiple chronic illnesses. In the Guided Care system, a single health care worker—typically a nurse—collaborates with several physicians to coordinate each patient’s care, ensuring that their needs are met and that various providers are not duplicating care or working at cross-purposes. A randomized trial found that the system improved the quality of patients’ care and tended to reduce the use of expensive services.

For the first two years of the model’s existence, Boult and his colleagues simply released it into the public domain, with no intention of patenting, trademarking or licensing it. Then he began to hear from federal agencies that other people around the country were claiming to use “Guided Care” in their grant applications—but drastically watered-down versions of Boult’s original model. “They were using ratios of one nurse to 500 patients, whereas the Guided Care model calls for ratios of 1 to 55,” Boult says. “They were basically going to erode the system’s credibility … it was a far less intensive intervention than what had been developed and tested.”

So in early 2009, Boult and his colleagues filed a disclosure with the Hopkins tech transfer office and began to secure their intellectual property. The process was a minor headache, he says, but his problem was solved. Whenever rogue versions of Guided Care emerge, the University’s tech transfer office sends a cease-and-desist letter.

At the same time, Boult has insisted on keeping the licensing fees low. (Depending on how many Guided Care nurses are employed, health care systems pay between $1,000 and $50,000 for a three-year license.) “This model was developed with taxpayer money, and I feel an obligation to make it available to American taxpayers,” Boult says. “If we’re licensing it in the United States, price should not be a barrier.”

Some activists at the Bloomberg School carry that sentiment further: They believe price shouldn’t be a barrier to Hopkins-generated innovations anywhere in the world. Kaci Hickox, who completed an MPH in December, has been a member of the Hopkins chapter of the University Alliance for Essential Medicines, an international campaign to ensure that medicines and medical devices are accessible in the developing world. “When I worked in Burma with Doctors Without Borders, I saw up close how important it is for people to have access to HIV medications,” Hickox says.

“What kind of biomedical scientist leaves the bench and goes around scrounging up funding and planning factories? But I actually see this as a continuation of my life’s work.”—Eddy Agbo

For the near term, the Hopkins chapter’s goal is to persuade the University to sign on to the Statement of Principles and Strategies for the Equitable Dissemination of Medical Technologies, which was developed by the Association of University Technology Managers. Universities that sign the statement pledge to develop licenses that “align incentives among all stakeholders to promote broad access to health-related technologies in developing countries.” Duke, Harvard, Yale and 23 other institutions have signed the pledge—but many others have not.

In response, Blakeslee says: “Hopkins is fully committed to the ideals of assuring that essential medicines are widely available.”

Across town at the University of Maryland Biopark, Eddy Agbo, PhD, DVM, reflects on his latest venture in business and life. A Nigerian-born biomedical researcher who was a research fellow at Johns Hopkins School of Medicine Agbo leads Fyodor (the small firm that is developing Sullivan’s urine-based malaria diagnostic).

“Ten years ago, this is something I never would have imagined myself doing,” says Agbo. “What kind of biomedical scientist leaves the bench and goes around scrounging up funding and planning factories? But I actually see this as a continuation of my life’s work. The only difference is that now, there’s a very targeted goal. We’re trying to bring some products to market and bring some tangible change to society.” Agbo hopes that someday these urine-based malarial diagnostics could be packaged together with small doses of medication, so that families could diagnose themselves at home and begin treatment promptly.

It has been a long road: Sullivan and his colleagues developed their diagnostic concept nearly a decade ago. “One thing I’ve learned is that you need to be patient,” says Sullivan. For now, he is doing what he knows best and sticking to his Hopkins lab. Among other things, he and his colleagues are combing through a huge library of drugs whose safety in humans has already been established, trying to learn if they might have effectiveness against rare diseases of the developing world.

If that research bears fruit, he will file a patent application—and steel himself for another decade of patience.