DECLARATION OF VENKATESH L. MURTHY, M.D., Ph.D.
`
`
`I, Venkatesh L. Murthy, declare as follows:
`
`
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`I have been retained by Jubilant DraxImage, Inc. (“Jubilant”) to offer
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`the instant declaration. I understand that Jubilant is petitioning the United States
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`Patent and Trademark Office for inter partes review of patents related to rubidium-
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`82 elution systems. I have been retained by Jubilant to explain, in this declaration,
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`medical uses of rubidium-82 and standard medical procedures therefor. I have not
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`been asked to analyze or provide legal opinions regarding any patent.
`
`I.
`
`INTRODUCTION AND QUALIFICATIONS
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`I am a board-certified physician in internal medicine and cardiovascular
`
`disease and an associate professor at the University of Michigan in its Department
`
`of Radiology, Divisions of Nuclear Medicine and Cardiothoracic Radiology, and
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`Department of Internal Medicine, Division of Cardiovascular Medicine.
`
`
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`I received a B.S. in Biology and a M.S. in Chemistry from the
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`Massachusetts Institute of Technology in 1996. I received a Ph.D. in Biophysics
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`and Biophysical Chemistry from Johns Hopkins School of Medicine in 2001 and a
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`M.D. from Johns Hopkins School of Medicine in 2004. I completed my Internal
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`Medicine Internship at Johns Hopkins Bayview Medical Center in 2005. In 2006, I
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`completed one year of Radiology Residency at the Mallinckrodt Institute of
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`JUBILANT EXHIBIT 1017
`Jubilant v. Bracco, IPR2018-01449
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`

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`Radiology at Barnes-Jewish Hospital. In 2008, I completed my Internal Medicine
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`Residency at Johns Hopkins Bayview Medical Center. Between 2008 and 2012, I
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`completed a Cardiovascular Medicine Fellowship and a Cardiovascular Imaging
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`Fellowship at Brigham & Woman’s Hospital. I hold a Level 3 certification from the
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`Certification Board in Nuclear Cardiology, a Level 2 Comprehensive certification
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`from the National Board of Echocardiography, and have completed Level 3 training
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`in Cardiovascular MRI. I am a Fellow of the American College of Cardiology, the
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`American Heart Association, and the American Society of Nuclear Cardiology.
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`
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`At the University of Michigan, between 2012 and 2017, I served as a
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`Clinical Assistant Professor in the Department of Radiology’s Division of Nuclear
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`Medicine and Cardiothoracic Radiology, and the Department of Internal Medicine’s
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`Division of Cardiovascular Medicine. Since 2017, I have served as a Clinical
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`Associate Professor in Department of Radiology’s Division of Nuclear Medicine
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`and Cardiothoracic Radiology, and the Department of Internal Medicine’s Division
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`of Cardiovascular Medicine. Since 2016, I also have served as the Director of
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`Cardiac PET Research at the Frankel Cardiovascular Center. I am a member of the
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`American College of Cardiology (2008), the Society of Cardiovascular Magnetic
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`Resonance (2006), the American Society of Nuclear Cardiology (2010), the
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`American Heart Association (2010), and the Society of Nuclear Medicine and
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`Molecular Imaging (2010). I serve as a reviewer, editor, or board member of more
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`than four dozen peer-reviewed journals in the areas of cardiology, nuclear medicine,
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`and related topics. I am an author of 96 peer-reviewed articles, many of which I was
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`the lead author. I am an author of several articles related to rubidium-82 elution
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`systems, including:
`
` Boyden, et al., “Risk stratification with myocardial perfusion Rb-82
`positron emission tomography,” Curr. Cardiovasc. Imaging Rep. v. 7,
`pp. 9266 (2014);
` Moody, et al., “Limitations of 82Rb weight-adjusted dosing accuracy
`at low doses,” J. Nuclear Cardiology, v. 24, pp. 1395-1401 (2017); and
` Lee, et al., “Optimization of temporal sampling for 82Rb myocardial
`blood flow quantification,” J. Nuclear Cardiology, v. 24, pp. 1517-29
`(2017).
`
`
`
`I have personal experience working with rubidium-82 elution systems.
`
`I first started working with rubidium-82 elution systems during my at Brigham &
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`Woman’s Hospital, which began in July 2008. There, I trained in the use of such
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`systems, particularly the Cardiogen-82® Infusion System, discussed below. As part
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`of my training, I reviewed journal articles describing medical applications of
`
`rubidium-82, and product documentation, describing operating procedures of the
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`Cardiogen-82® Infusion System, as it existed in 2008. Also, I received training from
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`faculty at Brigham & Woman’s Hospital regarding such procedures. Thus, I am
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`familiar with prevailing medical practices in 2008 generally and as they apply to
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`rubidium-82 elution systems.
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`
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`I have participated in approximately 3,000 to 4,000 rubidium-82 patient
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`elutions over my career. Since 2012, I have been responsible for training new
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`physicians in rubidium-82 elutions and supervising the rubidium-82 elution
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`procedures at the University of Michigan. The University of Michigan, where I am
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`employed, purchased rubidium-82 generators for the Bracco CardioGen-82
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`rubidium-82 elution system for over ten years, from 2007 to 2017. As such, I have
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`first-hand knowledge about the day-to-day operation of rubidium-82 elution
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`systems,
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`including
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`the
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`accepted practices
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`for
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`infusion of various
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`radiopharmaceutical agents for use in Positron Emission Tomography and the use of
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`rubidium-82 as one such radiopharmaceutical.
`
` My curriculum vitae, which is attached hereto as Exhibit A, contains a
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`more detailed description of my background.
`
`
`
`I am being compensated at my usual consulting rate of $500 per hour
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`for my technical analysis in this matter. My compensation is not contingent upon
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`the results of my work.
`
`II. OVERVIEW
`
`I was asked to provide an overview of the clinical and institutional use
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`of rubidium-82, and specifically, to explain the medical procedures used with
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`rubidium-82 chloride infusion systems as they existed prior to June 2008.
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` At a high level, rubidium-82 elution systems are employed in Positron
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`Emission Tomography (commonly, “PET”) systems, a type of nuclear molecular
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`imaging system. A rubidium-82 eluate is infused into a patient’s body, where it is
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`absorbed by cardiac tissue. The rubidium-82 eluate generates positrons as it decays,
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`which annihilate with electrons and emit a pair of photons in opposite directions.
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`The photons are captured by imaging equipment, a PET scanner, and an estimate of
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`the location of the rubidium-82 can be generated therefrom. Two-dimensional
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`and/or three-dimensional images of the absorption of rubidium-82 into cardiac tissue
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`may be generated from the PET scans.
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` Below, I provide an overview of nuclear imaging generally, an
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`introduction to rubidium-82 elution protocols and attendant risks, and an explanation
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`of medical procedures performed in 2008 to manage some of those risks. In this
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`discussion, I refer to several publications that describe these issues, as follows:
`
` Klein, “Precise 82RB
`infusion system for cardiac perfusion
`measurement using 3D positron emission tomography”, Ottawa-
`Carleton Institute for Electrical and Computer Engineering (Feb. 2005)
`(“Klein”);
` Chatal, et al., “Story of rubidium-82 and advantages for myocardial
`perfusion PET Imaging,” Frontiers in Medicine, v. 2, art. 65, pp. 1-7
`(Sept. 11, 2015) (“Chatal”);
` Alvarez-Diez, et al., “Manufacture of Strontium-82/Rubidium-82
`Generators and Quality Control of Rubidium-82 Chloride for
`Myocardial Perfusion Imaging in Patients using Positon Emission
`Tomography,” Applied Radiation and Isotopes, v. 50, pp. 1015-23
`(1999) (“Alvarez-Diez”);
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` Bracco CardioGen-82® Infusion System User’s Guide, Rev. 11 (July
`3, 2007) (“Infusion Manual”);
` Bracco CardioGen-82® Rubidium Rb 82 Generator, Rev. 43-8200
`(May 2000) (“Generator Manual”); and
` Implementation Guide for the Use of Bar Code Technology in
`Healthcare, HIMSS (2003) (“HIMSS”).
`III. HISTORY OF DEVELOPMENT AND USE OF RUBIDIUM-82 IN
`MEDICAL DIAGNOSTIC IMAGING
`A. Overview of Nuclear Molecular Imaging and Positron Emission
`Tomography
` Nuclear molecular imaging has been a leading medical diagnostic tool
`
`for decades, allowing clinicians to image physiological distribution of specific
`
`molecules within the body in a non-invasive manner. Klein at 4, Chatal at 1. In this
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`process, a compound labeled with a radioactive isotope (a “tracer”) is introduced
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`into a patient, usually by injection, and the tracer’s location is later imaged using a
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`scanner that is sensitive to radiation emitted by the tracer. Klein at 4.
`
` Different radioactive tracers are designed to concentrate in different
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`locations in a patient’s body by participating in the biochemical processes at those
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`locations. Klein at 4. Over time, the radioactive label in the tracer decays, resulting
`
`in the emission of radiation, which can be imaged. Id. As the tracer interacts with
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`the body, the concentrations of the tracer in those locations varies over time. Id.
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` When imaging a patient, tissues that contain high concentrations of a
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`tracer will radiate strongly compared to other tissues. A scanner that is capable of
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`detecting the radiation will measure the radiation and reconstruct tomographic
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`images (two-dimensional slices or sections) of the location of interest. Klein at 4.
`
`Because of the measureable change over time, the resulting images reflect the
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`biochemical and physiological processes within the body, as opposed to the
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`anatomical images produced by other techniques such as conventional x-ray
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`computed tomography (CT) and magnetic resonance imaging (MRI). Id.
`
` Radioactive material, in a closed system, experiences an exponential
`
`decrease in observed activity as time progresses. The rate of decay is a characteristic
`
`property of each radioactive isotope. Klein at 4. The average time required for the
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`activity to reach half of its original activity is referred to as the “half-life” of the
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`isotope, expressed as “T1/2,” and can vary from split seconds to years. Id.
`
` The half-life of a tracer dictates how much time can pass between
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`production of the tracer and the PET scan itself. Klein at 7. Tradeoffs exist between
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`short half-lives, which reduce patient and practitioner radiation exposure and
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`decrease the turnaround time between scans, and longer half-lives, which increase
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`the usable window of the tracer and the options available for producing the tracer.
`
`Klein at 7, Chatal at 1, 4.
`
`B. Medical Uses of Rubidium-82
` Medical applications of rubidium-82 first were uncovered in the 1950’s
`
`when it was discovered that biological behavior of rubidium was comparable to
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`potassium, and that its myocardial muscle uptake was proportional to blood flow in
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`coronary arteries. Chatal at 1. Thus, rubidium-82 can be used to image blood flow
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`to cardiac tissue.
`
` Preclinical studies were performed through the 1980s, primarily on
`
`dogs. Chatal at 1. In the 1980s, clinical studies were performed on hundreds of
`
`patients. Id. They demonstrated good diagnostic accuracy of rubidium-82 PET
`
`techniques, and superior performance to another technique, called technetium-
`
`99m/SPECT. Id.
`
`
`
`In 1989, the U.S. Food and Drug Administration (“FDA”) approved a
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`strontium-82/rubidium-82 generator, called the CardioGen-82®, for clinical use.
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`Klein at 7, Chatal at 1. Following FDA approval in 1989, the CardioGen-82® was
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`released to market and was utilized by many medical imaging centers and research
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`centers to generate rubidium-82 for patient infusion. Klein at 7, Chatal at 1. Thus,
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`rubidium-82 elutions were in medical use for almost 20 years prior to 2008 and
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`standard medical protocols were developed around the CardioGen-82® Infusion
`
`System.
`
` As noted, rubidium-82 can be used to image blood flow to cardiac
`
`tissue. Klein at 4. PET images will reflect the rubidium-82 uptake within the cardiac
`
`tissue, and inconsistencies in uptake can reflect cardiac impairments. Id. Thus, PET
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`scans can indicate abnormalities in blood flow to cardiac tissue and can lead to
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`diagnoses of cardiac conditions.
`
`C. Generating Rubidium-82
` Rubidium-82 can be generated at relatively low cost using a strontium-
`
`82/rubidium-82 generator which produces rubidium-82 as a byproduct of strontium-
`
`82 decay. Chatal at 4, Klein at 7-8. As strontium-82 decays within a strontium-
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`82/rubidium-82 generator, it generates rubidium-82 which remains bound to the
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`substrate. Id.. When a saline solution, such as 0.9% NaCl saline, is flushed through
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`the strontium-82/rubidium-82 generator, the rubidium-82 is displaced from the
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`substrate by sodium (Na) and the rubidium-82 (82Rb) is eluted in the form of 82RbCl
`
`(eluate) that can be infused into a patient. Id.
`
` Rubidium-82 has a relatively short half-life of 76 seconds, which is
`
`shorter than other tracers commonly used for medical imaging. Chatal at 4; Klein at
`
`7. For example, the technetium-99m used in the competitive SPECT technique has
`
`a half-life of 6 hours. Id. Because of rubidium-82’s short half-life, its effective
`
`radiation dose to patients and window of potential exposure to medical staff can be
`
`lower than for other tracers that have longer half-lives.
`
` Strontium-82, a required ingredient in a strontium-82/rubidium-82
`
`generator, has a relatively long half-life of 25.5 days. Klein at 8. As a byproduct of
`
`the strontium-82 production, strontium-85 (T1/2=64.8 days) is also produced. Id.
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`Although the strontium-85 is not beneficial for rubidium-82 production, it is difficult
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`to separate from strontium-82 and thus it is present in each batch of strontium-82
`
`created by a manufacturer. Id.
`
` Because of the strontium-82’s relatively long half-life, there is no need
`
`to produce the strontium-82 at a scanning site. Klein at 8. The strontium-
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`82/rubidium-82 generator may be manufactured at one location, then transported to
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`a scanning site where it would generate rubidium-82 for infusion into a patient.
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`Thus, use of a strontium-82/rubidium-82 generator permits use of PET scans at a
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`medical facility without incurring the expense of a cyclotron or other equipment that
`
`would be required to generate radioactive material on site. Rubidium-82, on the
`
`other hand, with its short 76 second half-life, must be produced at the scanning site
`
`using a generator. Chatal at 1, 4; Klein at 7.
`
` Prior to 2008, the CardioGen-82® Infusion System was a self-
`
`contained system that accepted a replaceable strontium-82/rubidium-82 generator.
`
`The strontium-82/rubidium-82 generator typically would be replaced every one to
`
`two months. As with many other medical systems, the CardioGen-82® Infusion
`
`System was provided as wheeled cart that permitted the CardioGen-82® Infusion
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`System to be moved about in a hospital environment. The CardioGen-82® Infusion
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`System also contained tubing circuits that were intended to be replaced every time
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`the strontium-82/rubidium-82 generator was replaced. Alvarez-Diez at 1020;
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`Infusion Manual at 1; Klein at 19-25.
`
`D. Risks Associated with strontium-82/rubidium-82 Generators,
`Including Strontium Breakthrough, and Controls Therefor
` The use of strontium-82/rubidium-82 generator systems and the related
`
`infusion systems presents certain risks. First, the strontium-82 material contained in
`
`the strontium-82/rubidium-82 generator, the strontium-85 material contained in the
`
`strontium-82/rubidium-82 generator, and
`
`the rubidium-82 eluate generated
`
`therefrom all are radioactive. It is extremely important to minimize radiation
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`exposure and to shield patients and medical personnel from inadvertent radiation
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`exposure at all times. For this reason, all rubidium-82 elution systems, including the
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`CardioGen-82® Infusion System and preclinical systems described in academic
`
`literature, possess extensive shielding. Generator Manual, p. 5; Klein at 8.
`
` Another risk associated with the use of strontium-82/rubidium-82
`
`generators to produce rubidium-82 eluate for infusion is the possibility of strontium
`
`“breakthrough.” Klein at 9. As saline is flushed through the strontium-82/rubidium-
`
`82 generator, some strontium (either strontium-82 or strontium-85) appears in the
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`eluate. Id. In high enough quantities, these compounds have adverse health effects
`
`because strontium is absorbed in bone, which surrounds bone marrow, and can cause
`
`increased risks of cancer. Id.
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` Various guidelines have been promulgated by different regulatory
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`agencies relating to guidelines for strontium exposure. By no later than 2005, Health
`
`Canada guidelines dictated that strontium-82 and strontium-85 breakthrough not
`
`exceed 20 Bq/MBq and 200 Bq/MBq respectively of the eluted rubidium-82activity.
`
`Klein at 9. Since at least as early as the 1990s, the U.S. Pharmacopeia has included
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`radionucleic purity specifications for rubidium chloride injections. 100O at 1392.
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`USP 23 specifies a maximum strontium-82 activity in rubidium-82 eluate (after 1
`
`hour of standing) of 0.02 kBq per MBq of rubidium-82 and a maximum strontium-
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`85 activity of 0.2 kBq per MBq of rubidium-82, the same as Health Canada. Id. The
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`Cardiogen-82® was approved by the FDA with the same limits. Generator Manual
`
`at 1.
`
`Id.
`
`“When eluted at a rate of 50 mL/minute, each generator eluate at the
`end of elution should not contain more than 0.02 microcurie of
`strontium Sr 82 and not more than 0.2 microcurie of strontium Sr 85
`per millicurie of rubidium chloride Rb 82 injection, and not more than
`1 microgram of tin per mL of eluate.”
`
`
`
`In order to minimize the risks associated with strontium breakthrough,
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`daily breakthrough tests were required to be performed before patient elutions could
`
`occur. These breakthrough tests tested a sample of eluate generated by an strontium-
`
`82/rubidium-82 generator using a radiation detector (or dose calibrator) to quantify
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`any strontium in the eluate before human use. Klein at 18, Generator Manual at 9;
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`Infusion Manual at 31.
`
` Prior to 2008, daily breakthrough tests for the CardioGen-82® Infusion
`
`System required a multistep manual process, as follows:
`
`a. flushing the generator with, for example, 50mL of saline at a rate of 50
`
`mL/min, and collecting a test sample of the eluate;
`
`b. measuring radiation activity of the test sample quickly after elution;
`
`c. allowing the test sample to stand for approximately 60 minutes;
`
`d. measuring radiation activity of the test sample after the 60 minute
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`standing period concludes.
`
`Generator Manual at 10. During the 60-minute period between the first
`
`measurement of radiation activity and the second measurement of radiation activity,
`
`radiation activity of the rubidium-82 decays to a negligible level. The activity that
`
`remains at the end of the 60-minute period reflects activity of the strontium-82 and
`
`the strontium-85. An operator calculates the strontium-82 and strontium-85
`
`breakthrough values from the recorded measurements and times and compares them
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`to designated limits. Id.
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` Once strontium breakthrough in a strontium-82/rubidium-82 generator
`
`exceeds regulatory limits, it cannot be stopped or reversed. The generator must be
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`replaced with a new strontium-82/rubidium-82 generator before patient elutions may
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`resume. By 2008, it was a standard medical practice to suspend all patient elutions
`
`when a strontium breakthrough event is detected, pending replacement of the
`
`strontium-82/rubidium-82 generator. For example, the CardioGen-82 user manuals
`
`make clear that patient infusion procedures are not to be performed unless the
`
`generator passes the daily strontium breakthrough test:
`
`PATIENT ADMINISTRATION MAY BE PERFORMED ONLY
`AFTER SUCCESSFUL COMPLETION OF DAILY CALIBRATION,
`SR-82/85 BREAKTHROUGH PROCEDURES, AND FIRST WASH
`(ELUTION) DISPOSAL USING SAME SETTINGS AS SEEN ON
`SR-82/85 BREAKTHROUGH SHEET PAGE.
`
`Infusion Manual at 31.
`
` Thus, by 2008, it was a standard medical practice to perform strontium
`
`breakthrough tests by hand on a daily basis prior to the first patient infusion of the
`
`day. It was also standard medical practice to disqualify a strontium-82/rubidium-82
`
`generator from further use if the generator failed a strontium breakthrough test, and
`
`the amount of strontium present in a test sample of eluate exceeded regulatory limits.
`
` Moreover, by 2008, it was a standard medical practice to create written
`
`records of all medical procedures performed on patients, and to create written
`
`records of all procedures performed to setup, calibrate, and approve medical
`
`equipment for daily patient use. The CardioGen-82® Infusion System was no
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`different. For example, the CardioGen-82® Infusion System user manual contained
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`a “CARDIOGEN® Rb-82 Generator Sr-82 Breakthrough Log Sheet” in which
`
`operators compiled data regarding results of the daily strontium breakthrough tests
`
`performed on individual generators. Infusion Manual at 38. The CardioGen-82®
`
`Infusion System user manual also contained an “Rb-82 Infusion System Calibration
`
`Log Sheet” in which operators logged generator performance data obtained from
`
`calibration infusions and calibration factors computed from that data. Infusion
`
`Manual at 37. The Breakthrough Log Sheet and the Calibration Log Sheet both were
`
`designed to be restarted for each generator received from the manufacturer, which
`
`identified its “Generator Lot Number.” Id., at 37-38.
`
`IV. STANDARD INFORMATION TECHNOLOGY PRACTICES IN
`MEDICAL FACILITIES
` By 2008, it was a standard medical practice to employ information
`
`technology systems to track patients, medical devices and medicines within medical
`
`facilities. See generally, HIMSS. For example, patients commonly were assigned
`
`bar-coded bracelets upon admission to a facility and their paper charts were given
`
`labels with the same bar coding. HIMSS, at 5-6. In this manner, when medicines
`
`were administered to a patient, the patient’s bar code would be scanned to generate
`
`a record of the event. See, HIMSS, at 6, 21. Moreover, when medical personnel
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`needed to review a patient’s medical file, the same bar code would be scanned to
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`retrieve the patient’s file.
`
` Medical devices and medicines also were assigned bar codes. HIMSS
`
`at ix, 6. By 2008, it was common use bar codes to track to a variety of healthcare
`
`assets including patient records, medications, reusable and disposable medical
`
`devices, blood and tissue specimens, and movable medical equipment. See, HIMSS,
`
`at 6, 21; see also, id. at Ch. 3-5. When medical personnel would retrieve medical
`
`devices from inventory at a facility, they would track their use by scanning the
`
`devices’ bar codes, as well as bar codes on a patient’s file or identification band.
`
`Similarly, medicines were assigned bar codes, which would be scanned upon
`
`retrieval from the pharmacy and administration to patients. Bar codes could contain
`
`a variety of information, including product identifiers, medication type, lot numbers,
`
`or patient data. I am not aware that the CardioGen-82® Infusion System had such
`
`capabilities, however.
`
`V. DECLARATION IN LIEU OF OATH
`
`In signing this declaration, I realize that this declaration will be filed as
`
`evidence in a contested case before the Patent Trial and Appeal Board of the United
`
`States Patent and Trademark Office.
`
`
`
`I am aware that willfully false statements and the like made by me in
`
`connection with this declaration are punishable by fine or imprisonment, or both (18
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`Page 16 of 17
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`U.S.C. § 1001) and may jeopardize the validity of the Petition. All statements herein
`
`made by me of my own knowledge are true and all statements made on information
`
`and belief are believed to be true.
`
`I declare under penalty of perjury that the
`
`foregoing is true and correct.
`
` nkatesh L. Murthy, M.D., Ph. D.
`
`Date: g'lbl'wl?
`
`

`

`
`
`
`Exhibit A
`
`Exhibit A
`
`
`
`

`

`Venkatesh L. Murthy, M.D., Ph.D.
`Associate Professor
`University of Michigan
`Department of Internal Medicine, Division of Cardiovascular Medicine
`Department of Radiology, Divisions of Nuclear Medicine and Cardiothoracic Radiology
`1338 Cardiovascular Center
`1500 E. Medical Center Drive, SPC 5873
`Ann Arbor, MI 48109
`Tel: (734) 936-5387 Fax: (734) 232-3246
`vlmurthy@med.umich.edu
`
`EDUCATION AND TRAINING
`9/1993 – 6/1996
`Massachusetts Institute of Technology, Bachelor of Science (Biology) &
`Master of Science (Chemistry)
`
`9/1996 – 5/2004
`
`Johns Hopkins School of Medicine, Doctor of Medicine (awarded 5/2004)
`& Doctor of Philosophy (Biophysics and Biophysical Chemistry, awarded
`2/2001), NIH Medical Scientist Training Program
`
`7/2004 – 6/2005
`
`Johns Hopkins Bayview Medical Center, Medicine Internship
`
`7/2005 – 6/2006
`
`Mallinckrodt Institute of Radiology, Barnes-Jewish Hospital, Radiology
`Residency
`
`7/2006 – 6/2008
`
`Johns Hopkins Bayview Medical Center, Medicine Residency
`
`7/2008 – 6/2011
`
`Brigham & Women’s Hospital, Cardiovascular Medicine Fellowship
`
`7/2010 – 8/2010
`
`Harvard School of Public Health: Program in Clinical Effectiveness
`
`7/2010 – 8/2012
`
`Brigham & Women’s Hospital, Cardiovascular Imaging Fellowship
`
`5/2011
`
`Brigham & Women’s Center for Clinical Investigation: Advanced
`Biostatistics for Medical Researchers
`
`9/2011 – 6/2012
`
`Harvard University Catalyst Program: Certificate in Applied Biostatistics
`
`5/2012
`
`Brigham & Women’s Hospital: Current Clinical Practice of Non-Invasive
`Vascular Diagnostic Imaging
`
`CERTIFICATION AND LICENSURE
`8/2008 – 12/2018
`American Board of Internal Medicine, Internal Medicine
`
`11/2011 – 12/2021
`
`American Board of Medicine, Cardiovascular Diseases
`
`1/2008 – 1/2017
`
`Drug Enforcement Administration, Controlled Substances Registration
`
`5/2008 – 3/2013
`
`Massachusetts Board of Registration in Medicine, Medical License
`
`5/2008 – 5/2014
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`Massachusetts Controlled Substances Practitioner
`
`7/2012 – 1/2019
`
`Michigan Medical License
`
`7/2012 – 1/2019
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`Michigan Controlled Substances License
`
`7/2012 – 6/2022
`
`National Board of Echocardiography, Level 2 Comprehensive
`
`1/2013 – 3/2023
`
`Certification Board in Nuclear Cardiology, Level 3
`
`Curriculum Vitae: Venkatesh L. Murthy
`
`8 June 2018
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`1 of 34
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`7/2012 – Present
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`Cardiovascular MRI, Level 3
`
`2/2014 – Present
`
`Fellow of the American College of Cardiology
`
`9/2014 – Present
`
`Fellow of the American Society of Nuclear Cardiology
`
`ACADEMIC, ADMINISTRATIVE AND CLINICAL APPOINTMENTS
`9/2017 – Present
`Clinical Associate Professor, Division of Cardiovascular Medicine,
`Department of Internal Medicine (Primary)
`
`9/2017 – Present
`
`9/2012 – 9/2017
`
`9/2012 – 9/2017
`
`Clinical Associate Professor, Divisions of Nuclear Medicine and
`Cardiothoracic Radiology, Department of Radiology (Secondary)
`
`Clinical Assistant Professor, Division of Cardiovascular Medicine,
`Department of Internal Medicine (Primary)
`
`Clinical Assistant Professor, Divisions of Nuclear Medicine and
`Cardiothoracic Radiology, Department of Radiology (Secondary)
`
`6/2016 – Present
`
`Director of Cardiac PET Research, Frankel Cardiovascular Center
`
`RESEARCH INTERESTS
`
`EMERGING NON-INVASIVE METHODS FOR CARDIOMETABOLIC RISK ASSESSMENT
`I am investigating a number of exciting new tools including the use of imaging (PET and CT) and
`serum biomarkers (ultrasensitive protein assays, microRNAs and metabolites) to non-invasively
`evaluate coronary vascular dysfunction, cardiovascular inflammation and autonomic
`dysfunction and their relationships with adiposity, obesity and cardiometabolic outcomes
`including metabolic syndrome, diabetes, renal failure, coronary heart disease and heart failure.
`
`EFFECTS OF ACCREDITATION, TRAINING AND CERTIFICATION ON QUALITY OUTCOMES IN
`CARDIAC IMAGING
`Accreditation is now mandatory in many imaging areas but requires substantial financial and
`time expenditures. We are utilizing Medicare data to evaluate the relationship between
`accreditation on patient-centered quality outcomes including revascularization. Similar
`approaches are also being used to investigate the effects of provider and staff training and
`certification.
`
`EARLY EFFECTS OF CHEST IRRADIATION ON CARDIAC STRUCTURE AND FUNCTION
`Together with colleagues in radiation oncology, we are investigating the effects of radiation
`therapy on coronary vasomotor function, myocardial edema, myocardial fibrosis and early
`markers of systolic dysfunction.
`
`GRANTS
`
`PRESENT AND ACTIVE
`5/15/2014 – 4/30/2019 P01CA059827 (PI: Theodore Lawrence)
`
`Optimization of high dose conformal therapy
`
`Curriculum Vitae: Venkatesh L. Murthy
`
`8 June 2018
`
`2 of 34
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`Role: Co-I on sub-project examining cardiac toxicity from lung radiation
`therapy
`
`1/1/2017 – 12/31/2018 Hope Foundation (PI: Laurence H. Baker)
`
`Sarcoma survivorship
`
`Role: Co-I
`
`4/1/2017 – 3/31/2019 Singulex (PI: Venkatesh Murthy)
`
`Coronary flow reserve PET biomarker study
`
`Role: PI
`4/1/2017 – 3/31/2022 1R01HL136685-01 (PI: Venkatesh Murthy and Ravi Shah)
`
`Molecular markers of early cardiometabolic health transitions in the
`CARDIA study
`Role: PI with Ravi Shah (multiple PI plan)
`
`1/1/2018 – 12/31/2018 Siemens Molecular Imaging (PI: Venkatesh Murthy)
`
`Advanced reconstruction and collimation for cardiac molecular imaging
`
`Role: PI
`7/1/2018 – 6/30/2023 R01AG059729 (PI: Venkatesh Murthy, Anne Newman and Ravi Shah)
`
`Implications of metabolism on healthy aging in African and Caucasian
`Americans: the Health ABC study
`Role: PI with Anne Newman & Ravi Shah (multiple PI plan)
`Percentile score of 2%, Impact score of 17
`
`
`
`
`PREVIOUS
`7/1/2014 – 6/30/2017 2014 Mitzi & William Blahd, MD, Pilot Research Grant
`
`Molecular imaging of inflammation in cardiac sarcoidosis
`
`Role: PI
`
`10/1/2014 – 9/31/2017 Breast Cancer Research Fund (PI: Lori Pierce)
`
`Biomarkers and cardiac MRI as early indicators of cardiac exposure
`following breast radiotherapy
`Role: Primary Co-I
`
`
`
`
`
`7/1/2016 – 6/30/2017 Frankel Cardiovascular Center Micro Grants (PI: Venkatesh Murthy, Roma
`Gianchandani and James Corbett)
`Use of continuous glucose sensors to improve throughput and safety of
`myocardial viability testing
`Role: PI
`
`
`
`1/1/2015 – 6/30/2017 Intersocietal Accreditation Commission Research Award
`
`IAC accreditation and the performance of stress testing in Medicare
`beneficiaries
`Role: PI
`
`
`
`4/1/2014 – 3/31/2017 Stuart and Barbara Padnos Breast Cancer Research Funds
`
`Cardiac MRI for evaluation of radiation-induced cardiotoxicity in breast
`cancer patients
`Role: Co-PI with Reshma Jagsi
`
`
`
`11/1/2012-10/31/2016 Gilead IN-US-259-0160 (PI: Marcelo Di Carli)
`
`Curriculum Vitae: Venkatesh L. Murthy
`
`8 June 2018
`
`3 of 34
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`Effects of ranolazine on myocardial blood flow in symptomatic patients
`with diabetes and suspected or known coronary artery disease
`Role: Consultant
`
`2/1/2015 – 1/31/2016 Michigan Translational Research and Commercialization Program
`
`18F-Hydroxyphenethylguanidines for PET quantification of cardiac
`sympathetic nerve density in patients with ischemic cardiomyopathy
`undergoing ICD implantation
`
`
`
`Role: Co-PI with David Raffel
`
`
`
`9/1/2014 – 8/31/2015 Michigan Translational Research and Commercialization for Life Sciences
`Kickstart Award (PI: David Raffel)
`Clinical translation of 18F-hydroxyphenethylguanidines for quantifying
`cardiac nerve density
`Role: Primary Co-I
`
`
`
`7/1/2014 – 6/30/2015 Radiology/Nuclear Medicine Seed Grants for Advancing Clinical Use of
`PET Radiopharmaceuticals
`Clinical translation of 18-F-labeled hydroxyphenethylguanidines for
`quantification of regional cardiac sympathetic nerve density with PET
`Role: Co-I with PI David Raffel
`
`
`
`
`
`7/2011 – 6/2013
`
`7/2010 – 6/2012
`
`9/1996 – 4/2004
`
`Brigham & Women’s Cardiovascular Leadership Council Award (PI: Usha
`Tedrow) Development of advanced tools for image guided
`electrophysiology interventions
`
`National Institutes of Health T32 HL094301 (PI: Marcelo Di Carli)
`Noninvasive Cardiovascular Imaging Research Training Program
`
`National Institutes of Health T32 GM007309 (PI: Stephen
`Desiderio/Robert Siliciano) Medical Scientist Training Program
`
`HONORS AND AWARDS
`1993
`National Merit Scholarship Finalist
`
`1993
`
`1994
`
`1995
`
`New York State Governor’s Excellence Award
`
`Massachusetts Institute of Technology, Robert A. Boit Writing Prize
`
`A