Recently, two exciting new patents were issued to Biophan Technologies, Inc. that will help revolutionize current devices. The first patented technology adds a monitoring signal to current devices to help detect fibrillation earlier. The second patented technology helps prolong battery life in devices. In addition, Dr. Spencer Rosero contributes new information about the temporary percutaneous pacing-defibrillation system.

Describe U.S. Patent 7,020,517 (“Fibrillation/Tachycardia Monitoring and Preventive System and Methodology). How does the technology work? How will incorporating a circuit prevent/detect the potential onset of ventricular fibrillation? What are some of the benefits of implementing this patent’s technology in devices?
       What this patent teaches is how to add new capabilities to both pacemakers and defibrillators. In the research that was done by Dr. Mark Spano and Dr. William Ditto, which came to my attention several years ago, I was quite surprised to learn that the change in the non-linear electrical signal of the heart was either inducing or occurring in parallel with ventricular fibrillation. By keeping the signal, which goes from a certain degree of inherent noise in the signal to less noise, it either induces or is an indication of fibrillation. Drs. Spano and Ditto were able to show in animal trials that if you kept the noisy component of the signal, you could potentially avoid the onset of fibrillation, and I thought that was a rather startling discovery.
       If you think about what a pacemaker does today, it is listening to the heart, and if the heart is beating too slowly, it puts forth a signal that causes the heart to beat faster. What a pacemaker doesn’t do, but an implantable cardioverter-defibrillator (ICD) does, is listen in case there is ventricular fibrillation and then put out a charge to recover the heart. Therefore, if you could detect the onset of this change in a very low-powered signal, and induce the noise that they describe in their experiment in an additional electrical circuit added to a pacemaker (which wouldn’t be a very expensive circuit — you wouldn’t need the powerful batteries or the powerful electronics needed to handle 800 volts, although you’d still be dealing with the typical 3-volt pacemaker) you could put a stochastic signal into that pacemaker lead and potentially avoid the onset of ventricular fibrillation. Now even if that occurred in only a small percentage of the total times that a person went into fibrillation, it might save lives. So for virtually no extra cost, you could theoretically improve pacemakers to begin to have a localized method of attacking ventricular fibrillation. To me this is an amazing potential. When I read their research, I started to write a patent to teach how to modify pacemakers to have this additional sensing and signal. That is the first part of what our new Biophan patent teaches.
       However, then it occurred to me that the same signal could have tremendous benefit in an ICD, because that is also monitoring the heart to see if there is an onset of fibrillation. By adding the monitoring circuit to detect the signal that precedes fibrillation, we can put in the stochastic signal when needed. If we see this early indicator of fibrillation and put in this stochastic signal — put in a little more noise than the heart’s electrical signal is inducing — we can avoid the onset of fibrillation and we can therefore avoid the need for the big shock. Obviously, for patients this would be a wonderful thing. They are not going to have the pain and discomfort when being shocked, as well as the potential of falling down when in fibrillation. It would make the defibrillator much less frightening for patients — some describe a particular anxiety about the potential of being shocked, and live in fear of the device going off. This patented technology would reduce the number of times that there is an onset of fibrillation.

For example, if the technology detects ventricular fibrillation, what is the sequence of events until the patient feels the first shock?
       Based on what Dr. Spano's papers taught, the technology will detect a signal before the ventricular fibrillation goes into full event — there will be a precipitory indicator. If you put this low stochastic noise into the heart signal, you may avoid the onset of ventricular fibrillation. Therefore, you would first let the system look for the early indicator that it doesn’t know to detect today. ICDs today monitor to see if: 1) the heart is okay, or 2) the heart is in fibrillation, which means the ICD is going to send a shock. This new patent would now be able to see that if this heart signal is changing, then your heart may be moving towards fibrillation. It can then correct it early by putting in more stochastic noise into the signal. This way, theorectically, the patient never feels anything and never goes into fibrillation at all. However, if the patient does ultimately go into fibrillation, the device still has ICD capabilities, so the ICD goes into normal function.
       My invention was to impose, into the normal functioning of the ICD, this additional sensing and signal, which is taught in the Spano papers as a signal that had been successfully demonstrated in animal studies. What I invented was how to apply it, in a pacemaker and a defibrillator design, as an improvement to the design functionality of the device. We filed our patent back in February 2004, having worked on it in 2003. The US patent was then granted to Biophan, so now if someone wants to go ahead and utilize this technology, we have the intellectual property to give them the incentive to be the first to market. We were pleased to read in the press that Medtronic had provided some funding to Dr. Spano and Dr. Ditto.

Is it compatible with current devices available on the market?
       Yes, I think that any of the pacemakers on the market today could be adapted relatively easy for this additional sensing and signaling circuit. In a minimum reprogram, they would potentially have some additional components, but it wouldn’t be very complicated or expensive to add this feature to a pacemaker or defibrillator at the manufacturing design level, and that’s our goal.
       We are in discussions right now with several pacemaker companies interested in the teaching of this patent, and we’re really encouraging them, because unfortunately the way things work in the world of innovation is if a good idea gets published in a scientific paper but never gets patented, it doesn’t give the kind of incentive for any of the manufacturers to go spend the money in exploratory time, design, animal testing, human testing and FDA approval in order to go to market. It is simply not enough incentive. The existence of a patent gives the manufacturer the incentive to be the first to market and to have some time in the market before they might wish to cross-license, etc. So that is what we are looking for, a partner who wants to work with us to develop this patent into a device, or, if someone is already working on it, they could license the technology. It is a great time for us because we are already in discussions with the majority of the pacemaker manufacturers about MRI safety technology; Boston Scientific had already licensed our technology, so they have the rights to make pacemakers, defibrillators and neurostimulators that are safe for MRIs using our technology and our patents. There is interest from other companies as well.
       Additionally, we have entered into commercial research development with the FDA to help establish guidelines that could be used by these standard-setting committees to have a better articulation of what exactly is needed to make a device safe for pacemakers and defibrillators in MRIs. This is separate from the patents mentioned, but we are working to help the industry transition, because it was our founding mission to make all medical devices safe for MRI, and we are very close to that goal now.

Temporary Percutaneous Pacing-Defibrillation System Overview

-By Spencer Rosero, MD, Assistant Professor of Medicine and Director of the Pacemaker Clinic; Co-Director of the Hereditary Arrhythmia Clinic of the University of Rochester Patients receive temporary pacing for one of two reasons: 1) to provide temporary support if their heart is beating too slowly or if it is stopping altogether — but when the patient recovers or their illness has resolved, they won’t require a permanent pacemaker; or 2) to provide a bridging mechanism to prevent the heart from beating too slowly in patients who will ultimately need a permanent pacemaker or equivalent device to survive but are too ill to receive a permanent device. The main issue with current temporary pacemakers is that they do not factor in higher risk patients who may be prone to rhythm abnormalities — including sudden cardiac death — in the hospital setting. Hospitals attempt to have external defibrillators available, especially in the intensive care unit, the emergency room, and a lot of the other critical areas in the hospital. The Percutaneous Temporary Pacemaker-Defibrillator (PTICD) works by building into a standard temporary pacing wire the ability to deliver defibrillation initially through that same wire in a very cost-effective manner, changing the box that is right outside the patient to provide standard pacing, defibrillation and anti-tachycardia pacing. The device functions very much like a permanent implantable defibrillator, and provides pacing that is painless to the patient. This will hopefully prevent them from going into ventricular fibrillation, which would require administering a shock. The device itself leads to a wire going through the vein into the heart through an introducer sheath, which also functions as a defibrillation electrode. The wire is then attached to a small pacing/defibrillation control box, which is comfortably worn as a holster or small patch to the outside surface of the skin. The patient would be monitored continuously for life-threatening rhythms, and pace them out if they happen (prior to needing a shock). If all else fails, the device will shock right away. While there is a relatively small number of patients in each hospital who would need this technology on a daily basis, nationwide the amount of patients add up, because this is a small but growing high-risk population. It consists of patients awaiting transplant who need but are not yet candidates for a permanent device for a variety of reasons (for example, patients who have an active infection or are too sick to have a permanent implantable defibrillator implanted). The percutaneous temporary pacemaker-defibrillator protects patients at risk for sudden cardiac death at a time when they are acutely ill. The technology would respond within seconds, and minimize the role of shocks during ventricular tachycardia by providing sophisticated anti-tachycardia pacing, which is currently only available in permanent implantable defibrillators (ICDs). There is a growing number of patients living with implantable cardiac rhythm devices and their potential complications including device recalls, infection, and lead malfunctions. Patients requiring extraction of a permanent system due to infection or who are in the immediate cardiac surgery post-operative period often need a temporary pacing system in place as a backup because they no longer have an implantable defibrillator or are recovering from surgery but still have to be in a hospital setting. This group of patients still needs some kind of device to protect them until they get a new permanent system or recover completely. The PTICD technology provides a bridge for those patients who want to be comfortable and have the protection of pacing as a backup. The temporary wire systems that providers are currently using have been around for a long time. We think our new temporary pacing-defibrillation system is the next step in improving patient safety. It would parallel the trend toward AEDs in the community. The next standard in pacing is that every high-risk patient will have a temporary wire that also has capabilities for defibrillation and anti-tachycardia pacing. The technology can be readily incorporated into existing practice. It also doesn’t change the way physicians put the device in — it is implanted exactly the same way. The difference is that there is a module, a component with a rechargeable battery on the outside surface of the skin. The device is portable, thus improving patient comfort. Also, physicians don’t have to learn a new technique to use it.

Describe the second patent (U.S. 7,054,686). How does it differ? How does it prolong the battery life of devices?
       The second patent was designed to try and improve the battery life efficiency of pacemakers, neurostimulators, and defibrillators — devices that send a signal to the heart to induce pacing. For a pacemaker, the current battery life is about 7 years. However, one of the hopes of all pacing companies is to add future functions — such as more sensing and more ability to communicate outside the body — and that is going to put a drain on battery life. Therefore, there is a dynamic tension in the pacemaker design world of how long these devices will last. For example, if they added a feature, but the battery life went from 7 years to 5 years, the company might not add that feature. In addition, if they had to add a bigger battery, they might not add the feature. So if you can show a way to make the current systems more efficient, that has potential utility. I believe the battery life of defibrillators is approximately 5 to 6 years, depending on the manufacturer, so a portion of that battery life is dedicated to the pacing circuit, and a portion of that is also dedicated to the defibrillator’s power needs. Any efficiency in these devices that are trying to maximize length of battery life has potential merit. This is one of the things that just came out of our design as we were working on pacing circuit. We’re hoping the industry will look at these innovations and determine their merit and utility.

When will the technology from these first two patents be available in devices?
       The first patented technology is currently being discussed with pacemaker manufacturers. As of yet, we haven’t had discussions with anyone about the second patent; it would be up to the pacemaker manufacturers to have a look at it and see if they feel it has utility, and there isn’t enough evidence yet to show that the shorter pacing posts are going to be effective. However, in the first patent (fibrillation device), there is a fair amount of evidence that this approach has real potential — so it is fairly significant. The second patent basically teaches a means of shortening pacing pulses in a way that may increase battery life. We’ve not yet had discussions about it — most of the interest has been on the fibrillation patent and on MRI safety. However, when talking with clients we let them know that this technology is there if they think it can be of help to them and their future designs.

There is also a third patent on the horizon, right? Are you at liberty to discuss this technology (U.S. Application 2004-0186545A1) yet? Briefly describe how this temporary pacing system works, and some of its benefits.
       This is the invention of Dr. Spencer Rosero, an electrophysiologist at the University of Rochester, who feels that for people in the ICU who are fitted with temporary pacemakers, their devices should also be fitted to include temporary defibrillators as well. However, the placing of the temporary leads has tended to be difficult to place properly. Therefore, he designed a system with an improved means of properly placing a temporary ICD — it is basically a way in which one can take the temporary pacing lead and adapt it to also serve as a temporary defibrillator lead. Dr. Rosero believes it would be far superior to the temporary pacemakers available today. What his patent teaches is an improved way to have a temporary pacing and ICD lead that is easier to properly position, and is designed in a way that is more effective for the temporary pacing function in the ICU. However, let me defer to Dr. Rosero for more information about the patent [see inset].

Biophan’s previous focus was to prevent device damage during MRI. How did your research for detecting ventricular fibrillation come about? Is this Biophan’s first venture into ventricular fibrillation prevention technology?
       It is. This came about when several of us who were interested in non-linear technologies found a series of compelling articles by Drs. Spano and Ditto. Reading them made me think of a great alternative for a pacing device to also have defibrillator potential. The potential for ventricular fibrillation prevention as well as a way for the defibrillators to also have a less disturbing means of avoiding defibrillation was tremendous. It seemed to me that putting this into an algorithm in a certain design would be a great benefit to these devices, so we filed a patent. Since due to our business we are already in communication with pacemaker manufacturers, it seemed like this was something that we could bring to their attention. However, we wanted to make sure we had an issued patent first.
       In addition, we are working on other projects which have gone outside the original focus of MRI safety. We have entered into development of MYO-VAD^™, which is a different type of ventricular assist device since it never comes in contact with circulating blood. It is a whole new class of cardiac circulatory support that solves many of the problems of existing ventricular assist devices. In its design, it will have an EP function as well. We have also developed technology for making stents visible under MRI, enabling detection of in-stent restenosis without an angiogram. Therefore, there are a number of technologies that have blossomed, and are now being considered by the pacemaker, defibrillator and neurostimulator companies.