In This Issue
The Bridge: 50th Anniversary Issue
January 7, 2021 Volume 50 Issue S
This special issue celebrates the 50th year of publication of the NAE’s flagship quarterly with 50 essays looking forward to the next 50 years of innovation in engineering. How will engineering contribute in areas as diverse as space travel, fashion, lasers, solar energy, peace, vaccine development, and equity? The diverse authors and topics give readers much to think about! We are posting selected articles each week to give readers time to savor the array of thoughtful and thought-provoking essays in this very special issue. Check the website every Monday!

Precision Medicine in Cardiology through Research, Innovation, and Intellectual Property

Monday, January 18, 2021

Author: Ik-Kyung Jang, Monica S. Jang, and Ronald M. Latanision

Over 4 million people are admitted to hospitals annually with a diagnosis of acute coronary syndrome (ACS), which includes unstable angina and acute heart attack. The three most common underlying mechanisms for ACS are plaque rupture (40–60 percent), plaque erosion (40–60 percent), and calcified plaque (10 percent) (figure 1).

Plaque rupture has been well characterized for several decades, but the diagnosis of plaque erosion in living patients became possible only in 2013 (Jia et al. 2013), based on the 1991 invention by an engineer at MIT, James Fujimoto, of optical coherence tomography (OCT), a high-resolution imaging technology (Huang et al. 1991).

Jang figure 1.gif

FIGURE 1 Three underlying mechanisms of acute coronary syndrome: plaque rupture, plaque erosion, and calcified plaque. Plaque rupture demonstrates discontinuation of the fibrous cap (arrows) and an empty cavity (asterisk), previously filled with lipid-rich necrotic core. Plaque erosion shows preserved vascular structure and lumen (the superficial endothelium—the innermost layer of the vessel wall—has peeled off). The protruding structures (arrows) are a platelet-rich thrombus (blood clot). Calcified plaque shows superficial calcification with low signal intensity (arrows), which differentiates calcified plaques from other types.

Compared to conventional intravascular ultrasound at a resolution of 150–250 microns, OCT has 10-fold higher resolution using a catheter-based system to achieve a resolution of 10–15 microns. This enables visualization of the microarchitecture of a vessel wall, including atherosclerotic plaques. As a result, it is now known that plaque erosion has three distinct morphological characteristics: preserved vascular integrity, a larger vessel lumen, and a platelet-rich thrombus (blood clot; figure 1).

Although it is now understood that the three ACS conditions have distinctly different pathobiology, patients are treated uniformly with a coronary stent. Complications with stents are a major problem, however; renarrowing occurs in 10–40 percent of patients even with a drug-coated stent. Another catastrophic complication, stent clotting, can occur even after many years; the majority of these patients experience heart attack with a high mortality rate.

A proof-of-concept study (Partida et al. 2018) found that treatment with antithrombotic medications may be an option, avoiding use of a coronary stent in ACS patients with plaque erosion. OCT imaging and other technologies may yield additional effective treatments.

Technology for Precision Medicine:
What’s Needed

The OCT imaging–based approach is one of the first attempts toward precision medicine in cardiology, making it possible to tailor therapy based on an individual’s underlying pathobiology rather than applying uniform treatment to all patients with the same clinical diagnosis.

A key technology that is not yet available is a noninvasive imaging test that can identify plaque erosion. In the future, when a patient presents to an emergency department, the probability of plaque erosion could be estimated using simple clinical and laboratory tests, and confirmed by a noninvasive imaging test. If the test shows plaque erosion, the patient can be triaged to a conservative treatment and avoid invasive procedures.

If the findings of the plaque erosion study (Partida et al. 2018) are replicated using this noninvasive test in large-scale studies, the management of millions of ACS patients around the globe may be improved. Such a revolution will be possible through collaboration among engineers, technology transfer professionals, entrepreneurs, and physician-scientists—and can likely be achieved within the next 10 years.

The Changing Landscape of Patents and Technology Transfer

Historically in technology transfer, entrepreneurship, and innovation, patents have been considered the most prized form of intellectual property. But recently both academic and commercial technology transfer practices have recognized and begun capturing the value inherent to data and know-how.

A patent owner has the right to exclude others from making, using, importing, and selling a patented innovation for a limited term unless authorized under a patent license agreement. Such licenses are neither easy to negotiate nor free, but it is through licensing that academic technologies have not only penetrated but also in some cases determined the market.

Important technology gaps—such as a noninvasive imaging test that can identify coronary plaque erosion—need to be bridged.

Moreover, through licensing, among other types of agreements (e.g., sponsored research, codevelopment), research has expanded its economic and social footprint and incentivized further innovation. Not often is the relationship between science and economic interests in such lockstep.

Although the space for US patent protection may be decreasing and/or the threshold for patent eligibility increasing, there has been a shift toward codifying other forms of intellectual property, such as data and know-how.

Data

Data, which can encompass study results, patient data by indication, images, usage data, and analytics (among many other forms), have not traditionally been identified for their monetary value. But the recent impact of data analytics, evolving algorithms, and machine learning across many specialties, including cardiology, is undeniable.

Medical data can be used to develop, train, improve, and validate algorithms, and associated or resulting software can be categorized as an FDA approval–required medical device, which can change paradigms of clinical practice and contribute to evidence-based medicine. The data are not subject to patent protection costs, but they do come with privacy protection concerns (e.g., HIPAA, the EU General Data Protection Regulation), which are not trivial.

Data are invaluable and could lead to the next big diagnostic, preventive, or therapeutic modality. To that end it will be important to identify the most efficient ways to gather, organize, store, and transfer data in a -manner compliant with all applicable laws and regulations.

Know-How

Know-how has typically been shared freely in the academic community or pursuant to a consulting agreement with a commercial partner. Most consulting agreements stipulate that any intellectual property (know-how, patents, or otherwise) that arises from the consultation belongs to the commercial partner.

In academia, consulting agreements do not usually fall under the purview of a technology transfer office, as they pertain to intellectual property that does not belong to the academic institution. Only relatively recently have academic institutions recognized know-how as a significant and proprietary asset—and one that has been leaking out the “back door” of consulting agreements.

Licenses vs. Patents

Unlike patents, neither data nor know-how (or copyright, for that matter), provided they are properly protected, incur the same costs or come with an expiration date. They can therefore be used to extend the royalty-bearing term under a license well past the term of a patent and they can be licensed to more than one party (in contrast to know-how captured in a one-time consulting agreement).

Conclusion

The dichotomy between the approaches to data and know-how in academia and industry needs to be reconciled in order to benefit research and innovation, and this is the responsibility of technology transfer professionals. In the meantime, crucial technology gaps—such as a noninvasive imaging test that can identify plaque erosion—need to be bridged.

Innovators in both academia and industry are necessary to advances in all fields, including patient care. They, and engineers and physician-scientists, need to identify data and know-how and to work with their technology transfer office to codify the values of these assets—not just economically but, more importantly, for their potential scientific and social impacts.

References

Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Fujimoto JG. 1991. Optical coherence tomography. -Science 254(5035):1178–81.

Jia H, Abtahian F, Aguirre AD, Lee S, Chia S, Lowe H, Kato K, Yonetsu T, Vergallo R, Hu S, and 20 others. 2013. In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography. Journal of the American College of Cardiology 62(19):1748–58.

Partida RA, Libby P, Crea F, Jang IK. 2018. Plaque erosion: A new in vivo diagnosis and a potential major shift in the management of patients with acute coronary syndromes. European Heart Journal 39(22):2070–76.

 

About the Author:Ik-Kyung Jang is a cardiologist at Massachusetts General Hospital and the Allan and Gill Gray Professor of Medicine at Harvard Medical School. Monica Jang is licensing manager at Boston Children’s Hospital of Harvard Medical School and a candidate for JD (’23) at the University of New Hampshire Franklin Pierce School of Law. Ron Latanision (NAE) is the Shell Professor of Materials Science and Engineering (Emeritus), Massachusetts Institute of Technology, and a senior fellow at Exponent.