UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`JUBILANT DRAXIMAGE INC.,
`Petitioner,
`v.
`
`BRACCO DIAGNOSTICS INC.,
`Patent Owner.
`
`U.S. Patent Nos. 9,229,467 and 9,299,468
`
`Case Nos. IPR2018-01448, -01449, and -01450
`
`DECLARATION OF NORBERT J. PELC, Sc.D.
`
`Bracco Ex. 2003
`Jubilant v. Bracco
`IPR2018-01449
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`JUBILANT DRAXIMAGE INC.,
`Petitioner,
`v.
`
`BRACCO DIAGNOSTICS INC.,
`Patent Owner.
`
`U.S. Patent Nos. 9,229,467 and 9,299,468
`
`Case Nos. IPR2018-01448, -01449, and -01450
`
`DECLARATION OF NORBERT J. PELC, Sc.D.
`
`Bracco Ex. 2003
`Jubilant v. Bracco
`IPR2018-01449
`
`
`
`
`
`
`
`I.
`
`Contents
`
`INTRODUCTION AND QUALIFICATIONS .............................................. 1
`II.
`III. REAFFIRMATION OF PRIOR TESTIMONY ............................................. 4
`IV. RELATIONSHIP BETWEEN THE ’467 AND ’468 PATENT AND
`THE ITC PATENTS....................................................................................... 4
`V. MATERIALS CONSIDERED ....................................................................... 6
`VI. LEGAL STANDARDS ................................................................................ 11
`VII. TECHNOLOGICAL BACKGROUND AND OVERVIEW OF THE
`IPR PATENTS .............................................................................................. 12
`VIII. POSITA ........................................................................................................ 15
`IX. CLAIM CONSTRUCTION ......................................................................... 17
`X.
`THE PRIOR ART ......................................................................................... 20
`A. Klein ................................................................................................... 22
`B.
`FDG systems ...................................................................................... 32
`C.
`Tate and Reilly are FDG systems ....................................................... 33
`D.
`Tate and Reilly are not suitable for 82Rb elution-infusion ................. 34
`E.
`Reilly does not disclose a moveable cart ........................................... 39
`XI. A POSITA WOULD NOT MOVE KLEIN’S DOSE CALIBRATOR
`ONTO KLEIN’S CART ............................................................................... 41
`XII. KLEIN’S COMPUTER DOES NOT PREVENT PATIENT
`INFUSION PROCEDURES IF A STRONTIUM BREAKTHROUGH
`TEST RESULT EXCEEDS AN ALLOWABLE LIMIT............................. 51
`XIII. AUTHENTICATION OF CAPINTEC USER MANUALS ........................ 62
`XIV. CONCLUDING STATEMENT ................................................................... 64
`
`
`ii
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`
`I, Norbert J. Pelc, declare as follows:
`
`II.
`
`INTRODUCTION AND QUALIFICATIONS
`1.
`I have been engaged by Patent Owner Bracco Diagnostics, Inc.
`
`(“Bracco”) to opine on certain matters regarding U.S. Patent Nos. 9,299,467 (“’467
`
`patent”) and 9,299,468 (“’468 patent”), together the “IPR patents”, relative to Inter
`
`Partes Review Nos. 2018-01448, -01449, and -1450 (“the IPRs”). Specifically, this
`
`Declaration addresses arguments made by Petitioner, Jubliant Draximage, Inc. in the
`
`IPRs regarding the validity of certain claims of the ’467 and ’468 patents.
`
`2.
`
`I am a Professor of Bioengineering, Radiology, and, by courtesy, of
`
`Electrical Engineering at Stanford University in Stanford, California.
`
`3.
`
`In 1974, I received my B.S. in Applied Mathematics, Engineering and
`
`Physics from the University of Wisconsin in Madison and I started my graduate
`
`studies at Harvard University. While a student at Harvard, I was a research assistant
`
`at the Massachusetts General Hospital (“MGH”). I received my S.M. in Medical
`
`Radiological Physics in 1976 and my Sc.D. in Medical Radiological Physics in 1979,
`
`both from Harvard University.
`
`4.
`
`I have worked in diagnostic imaging for more than 40 years. My
`
`graduate research while at Harvard and MGH focused on tomographic imaging with
`
`radioisotope sources (what is now called “Positron Emission Tomography” or PET),
`
`1
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`as well as tomographic imaging using x-ray sources (both “Computed Tomography”
`
`or CT, and what is now called “tomosynthesis”). From 1978 until 1990 I worked at
`
`GE Medical Systems as a Senior Physicist in the Radiological Sciences Laboratory,
`
`and as the manager of that group. While at GE, I contributed to the development of
`
`CT, Digital Radiography, Magnetic Resonance Imaging (MRI), and other advanced
`
`diagnostic imaging devices, and I collaborated with radiologists at leading medical
`
`centers on the development of new applications of these technologies.
`
`5.
`
`I joined Stanford University as an Associate Professor of Radiology in
`
`1990 and became a Professor of Radiology in 1997, a position I still hold. In 2002,
`
`I was named the Associate Chair for Research in the Department of Radiology. In
`
`2004, I was appointed Professor of Bioengineering, a position I also still hold. Since
`
`1990 I have also held a courtesy faculty appointment in Electrical Engineering at the
`
`same rank as my appointments in Radiology and Bioengineering. In 2012, I was
`
`named the Chair of the Department of Bioengineering and gave up the position of
`
`Associate Chair of the Department of Radiology. I completed my term as Chair of
`
`Bioengineering in 2017.
`
`6.
`
`I am named as an author on more than 200 published peer-reviewed
`
`journal articles and over 350 research papers presented at scientific conferences,
`
`essentially all in the field of diagnostic imaging, including Positron Emission
`
`2
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`Tomography. I am also named as an inventor on 95 issued U.S. Patents. Among
`
`these are contributions related to Positron Emission Tomography.
`
`7.
`
`I have received many awards for my contributions to medical imaging.
`
`I was elected to the National Academy of Engineering in 2012. In 2016, I received
`
`an Honorary Doctor of Medicine from Friedrich Alexander University of Erlangen-
`
`Nuremberg. I received the Edith H. Quimby Award from the American Association
`
`of Physicists in Medicine (AAPM) and the Outstanding Researcher Award from the
`
`Radiological Society of North America (RSNA), both in 2013. Among other honors,
`
`I am a Fellow of the AAPM, the International Society for Magnetic Resonance in
`
`Medicine, the Institute for Medical and Biological Engineering, and SPIE
`
`(international society for optics and photonics).
`
`8.
`
`I also served as a reviewer for the National Institutes of Health (NIH),
`
`including as a member of the Radiology and Nuclear Medicine Study Section of NIH
`
`from 1991-1997, and for other grant funding agencies. My additional NIH service,
`
`includes serving as a member of the National Advisory Council of the National
`
`Institute of Biomedical Imaging and Bioengineering and of the Council of Councils.
`
`I have served as a reviewer and on the editorial boards for many journals. I recently
`
`completed a term as the Editor-in-Chief of the Journal of Medical Imaging.
`
`9.
`
`A copy of my Curriculum Vitae (“CV”) is submitted herewith as
`
`3
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`Appendix A, which describes my education, training and experience in greater
`
`detail. Attached to my CV is a list of publications I have authored, including
`
`publications I have authored within the past ten years.
`
`10.
`
`I am billing my work in this matter at $695 per hour, with
`
`reimbursement for actual expenses. My payment is not contingent upon my
`
`testimony or the outcome of the case. I have no personal interest in the outcome of
`
`the case.
`
`III. REAFFIRMATION OF PRIOR TESTIMONY
`11. Aside from being engaged by Bracco for these IPRs, I was also engaged
`
`by Bracco in related ITC proceedings, i.e., U.S. International Trade Commission
`
`Investigation No. 337-TA 3303. I hereby reaffirm my testimony from the ITC
`
`proceedings, including the testimony listed below:
`
`Description
`Exhibit
`ITC Expert report of Dr. Norbert Pelc (Redacted)
`2011
`ITC Trial Testimony of Dr. Norbert Pelc (Public Version)
`2012
`ITC Trial Exhibits of Dr. Norbert Pelc (Redacted)
`2013
`IV. RELATIONSHIP BETWEEN THE ’467 AND ’468 PATENT AND THE
`ITC PATENTS
`12. As noted above, I understand that Petitioner has filed two IPRs against
`
`the ’468 patent and one IPR against the ’467 patent (collectively the “IPR patents”).
`
`As noted above, I have previously given testimony in an ITC proceeding regarding
`
`U.S. Patent Nos. 9,750,869, 9,750,870, and 9,814,826 (collectively the “ITC
`
`4
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`patents”). It is my understanding that the IPR patents and the ITC patents have
`
`generally the same specification, but different claims. It is also my understanding
`
`that both the IPR patents and the ITC patents claim priority back to a common PCT
`
`patent application filed June 11, 2009, and therefore all of the IPR and ITC patents
`
`are at least entitled to a priority date of June 11, 2009. (See, e.g., Ex. 2011 at ¶53-
`
`56.)
`
`13. The “Klein Thesis” reference cited in the ITC proceeding is the same
`
`Klein Thesis cited in the IPRs, i.e., Ran Klein, “Precise 82Rb Infusion System for
`
`Cardiac Perfusion Measurement Using 3D Positron Emission Tomography,”
`
`Ottawa-Carleton Institute for Electrical and Computer Engineering (Feb. 2005) (the
`
`“The Klein Thesis” or “Klein”).
`
`14. The “Tate” reference cited in the ITC proceedings is the same Tate
`
`reference cited in the IPRs, i.e., U.S. Patent Application Publication No.
`
`2008/0177126, filed October 31, 2007 and published July 24, 2008.
`
`15.
`
`I further understand that many of the arguments made by Petitioner in
`
`the IPRs were also made by Petitioner in the ITC (e.g., the claims are obvious based
`
`on Klein plus Tate; Klein discloses a computer that prevents patient infusions if the
`
`results of a breakthrough test exceed an allowable limit).
`
`16. Based on the foregoing, in the interest of efficiency, I sometimes refer
`
`5
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`US. Patent Nos. 9,299,467 and 9,299,468
`
`to my ITC testimony herein to support my opinions in the IPRs.
`
`17.
`
`Further, when referring to the specifications of the IPR patents, I
`
`sometimes just cite to either the ’467 patent or the ’468 patent, understanding that
`
`the same disclosure occurs in the non-cited patent.
`
`V. MATERIALS CONSIDERED
`
`18.
`
`The analysis that I provide in this Declaration is based on, inter alia,
`
`my experience, the prior testimony I have provided in the related ITC proceedings,
`
`and pertinent documents from the IPRs. Below is a non-exhaustive list of the
`
`materials I have considered relative to the IPRs.
`
`Description
`
`IPR2018—01448,
`-0l450
`
`IPR2018—01449
`
`Petition for Inter Parties Review
`
`
`
`Institution Decision
`
`US. Patent No. 9,299,468
`468 . atent”
`
`US. Patent No. 9,299,467
`467 . atent”
`
`Prosecution History of US.
`Patent Application No.
`1 2/ 1 3 7,3 56
`
`Prosecution History of US.
`Patent Application No.
`1 2/ 1 3 7,3 77
`
`Prosecution History of US.
`Patent Application No.
`1 2/ 1 3 7,3 63
`
`Prosecution History of US.
`Patent Application No.
`12/ 1 37,3 64
`
`Pa o er 01
`
`Pa 0 er 07
`
`Ex. 1001
`
`N/A
`
`N/A
`
`Ex. 1001
`
`Ex. 1006
`
`Ex. 1007
`
`Ex. 1008
`
`Ex. 1009
`
`
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`US. Patent Nos. 9,299,467 and 9,299,468
`
`Description
`
`IPR2018—01448,
`—014S0
`
`IPR2018—01449
`
`Prosecution History of US.
`Patent Application No.
`1 2/808,467
`
`Prosecution History of US.
`Patent Application No.
`14/455,63 1
`
`Prosecution History of US.
`Patent Application No.
`14/455,623
`
`Alvarez-Diez, “Manufacture of
`strontium-82/rubidium—82
`
`generators and quality control of
`rubidium-82 chloride for
`
`myocardial perfusion imaging in
`patients using positron emission
`tomography,” Applied Radiation
`and Isotopes, V. 50, pp. 1015—23
`1999
`
`Klein et a1, “Precision Control of
`
`Eluted Activity from a Srmb
`Generator for Cardiac Positron
`
`Emission Technology,” Engr. In
`Med. and Biology Soc. 26th
`Annual International Conference
`
`of the IEEE, vol. 1, pp. 1393-
`1396 2004
`
`Ran Klein, “Precise 82Rb
`
`Infusion System for Cardiac
`Perfusion Measurement Using
`3D Positron Emission
`
`Tomography,” Ottawa-Carleton
`Institute for Electrical and
`
`Computer Engineering (Feb.
`2005) (“The Klein Thesis” or
`“Klein”
`
`
`
`Ex. 1010
`
`BX. 101 1
`
`N/A
`
`N/A
`
`Ex. 101 l
`
`Ex. 1012
`
`Ex. 1013
`
`EX. 1014
`
`
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`US. Patent Nos. 9,299,467 and 9,299,468
`
`Description
`
`IPR2018—01448,
`—01450
`
`IPR2018—01449
`
`PDle-(garation ofRobert T. Stone,
`
`Ex. 1015_,468
`
`Ex. 1015_,467
`
`
`
`Declaration of Ventakesh
`
`Murth , M.D.
`
`Barker, et al., US. Patent
`4,585,009, granted April 29,
`1 986
`
`US. Pharmacopeia 23 National
`Formul.
`18 1995
`
`Bracco CardioGen-82® Infusion
`
`System User’s Guide, Rev. 07
`(July 20, 2004) (“The Bracco
`Manual”
`
`Hirschman, et al., US. Patent
`
`Publication No. 2011/0178359,
`
`filed December 28, 2007
`“Hirschman”
`
`Jackson, et al., US. Patent
`
`Publication No. 2008/024291 5,
`
`filed March 2, 2004 and
`
`published October 2, 2008
`“Jackson”
`
`Reilly, et al., US. Patent
`Publication No. 2004/0260143,
`
`published December 23, 2004
`“Reill ”
`
`Tate, et al., US. Patent
`
`Publication No. 2008/0177126,
`
`filed October 31, 2007 and
`
`ublished Jul 24, 2008 “Tate”
`
`Chatal, et al., “Story of
`rubidium—82 and advantages for
`myocardial perfusion PET
`Imaging,” Frontiers in Medicine,
`V. 2, art. 65, pp. l-7 (Sept. 11,
`2015
`“Chatal”
`
`EX. 1017
`
`EX. 1018
`
`Ex. 1019
`
`Ex. 1021
`
`Ex. 1022
`
`Ex. 2001
`
`Ex. 1023
`
`N/A
`
`Ex. 1024
`
`N/A
`
`Ex. 1025
`
`Ex. 1022
`
`EX. 1026
`
`Ex. 1025
`
`
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`US. Patent Nos. 9,299,467 and 9,299,468
`
`Description
`
`IPR2018—01448,
`—01450
`
`IPR2018—01449
`
`Bracco CardioGen—82®
`
`Rubidium Rb 82 Generator, Rev.
`43-8200 (May 2000)( “Bracco-
`
`2000”)
`ISO 13485:2003 — Medical
`
`Ex. 1026
`
`EX. 1027
`
`Devices — Quality Management
`Systems — Requirements for
`Regulatory Purposes (July,
`2003)
`“13013485”
`
`21 CFR Part 820.1 (2005)
`‘(CFR820- 1,,
`
`EN 6227422005 — Medical
`
`Electrical Equipment — Safety of
`Radiotherapy Record and Verify
`Systems (December 28, 2005)
`“EN62274”
`
`21 CFR Part 11.] (2004)
`“CFRl 1.1”
`
`10 CFR Part 20 (10 CFR
`20.1001-2 “CFR20.1001-2”
`
`10 CFR Part 20 (10 CFR
`20.1003
`“CFR20.1003”
`
`The Chemical Rubber Co.,
`Handbook of Radioactive
`
`Nuclides, Yen Wang ed., 1969
`“ChemRubberl 969
`
`Bates et al. “Effect of
`
`computerized physician order
`entry and a team intervention on
`prevention of serious
`medication,” JAMA, vol.
`
`280(15), pp.1311-6 (Oct. 21,
`1998
`“Batesl”
`
`Bates et al. “The impact of
`comuterized h sician order
`
`EX" 1028
`
`Ex. 1023
`
`EX- 1029
`
`EX. 1024
`
`EX. 1030
`
`Ex. 1029
`
`Ex. 1031
`
`N/A
`
`Ex. 1032
`
`Ex. 1027
`
`EX. 1033
`
`Ex. 1028
`
`Ex. 1034
`
`Ex. 1030
`
`Ex. 1035
`
`N/A
`
`Ex. 1036
`
`N/A
`
`
`
`
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`US. Patent Nos. 9,299,467 and 9,299,468
`
`Description
`
`IPR2018—0l448,
`-0l450
`
`IPR2018—01449
`
`entry on medication error
`prevention,” J Am Med Inform
`Assoc. l999;6(4):313—321
`
`(“Bates2”)
`Defense Information Systems
`Agency — Medical Devices
`Security Technical
`Implementation Guide, version
`1, release 1, 27 July 2010
`“Defense2010”
`
`Ex. 1037
`
`N/A
`
`
`
`HIMSS, “Implementation Guide
`for the Use of Bar Code
`
`Ex. 1038
`
`N/A
`
`Technology in Healthcare”
`
`(2003)(“HIMSS”)
`deKemp, US. Patent Publication
`No. 2007/0213848
`
`Ex. 1040
`
`Ex. 1033
`
`“deKem . ’ 848”
`
`deKemp, US. Patent Publication
`No. 2007/0140958
`
`“deKem . ’95 8”
`
`US. Patent No. 6,767,319 to
`
`Reill et a1.
`
`Comparison of US. Patent
`No. 6,767,319 to US. Patent
`Application Publication No.
`2004/0260143 to Reill et al.
`
`ITC Deposition of Dr. Robert
`Stone, October 9, 2018
`Redacted
`
`ITC Deposition of Dr. Robert
`Stone, October 10, 2018
`Redacted
`
`ITC Trial Testimony of Dr.
`Robert Stone, April 15, 2019
`Public Version
`
`Ex. 1041
`
`Ex. 1034
`
`Ex. 2001
`
`N/A
`
`Ex. 2002
`
`N/A
`
`EX- 2004
`
`Ex- 2005
`
`Ex- 2006
`
`10
`
`
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`US. Patent Nos. 9,299,467 and 9,299,468
`
`Description
`
`IPR2018—01448,
`—01450
`
`IPR2018—01449
`
`ITC Trial Testimony of Dr.
`Robert Stone, April 16, 2019
`Public Version
`
`Errata of Dr. Robert Stone
`
`regarding Ex. 1015 of IPRs
`2018-01448,
`—01449, and —01450
`
`Exhibit from Deposition of Dr.
`Robert Stone in IPRs 2018-
`
`01448, —01449, and —01450
`
`Deposition testimony of Dr.
`Robert Stone in IPRs 2018-
`
`01448, -01449, and —01450
`
`ITC Corrected Expert Report of
`Dr. Norbert Pelc Redacted
`gfiblflafiftfififiz32215,.
`LEEDEEESLKZ’S‘ °fDr'N°‘be“
`figflifigffifi‘m US“
`CAPINTEC CRC-lSR User
`Manual, Jul 2007
`
`
`
`VI. LEGAL STANDARDS
`
`Ex. 2007
`
`EX. 2008
`
`Ex. 2009
`
`Ex. 2010
`
`EX- 2011
`Ex. 2012
`Ex. 2013
`Ex. 2014
`Ex. 2015
`
`
`
`19.
`
`For the purposes of these inter partes reviews, I understand that the
`
`applicable legal standards regarding anticipation and obviousness are the same as
`
`recited in my ITC Expert Report (Ex. 2011) at 111125-26 and 30-35.
`
`20.
`
`For the purposes of these inter partes reviews, I understand that
`
`Petitioner Jubilant Draximage bears the burden of showing, by a preponderance of
`
`11
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`the evidence, invalidity of any claims it challenged.
`
`VII. TECHNOLOGICAL BACKGROUND AND OVERVIEW OF THE IPR
`PATENTS
`21. The IPR patents disclose computer-facilitated maintenance and
`
`operation of systems that generate and infuse radiopharmaceuticals (e.g., rubidium-
`
`82, 82Rb) into patients for the purpose of PET imaging. The system 10 (pictured
`
`below) includes shell 13, with a generator 21 located therein (not visible in this
`
`picture; shown in Fig 3A of the IPR patents).
`
`22. Generally, maintenance
`
`and
`
`operational
`
`procedures
`
`for
`
`radiopharmaceutical generating and infusion systems may be complex, especially
`
`
`
`12
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`given safety and efficacy concerns when handling radioisotopes. The IPR patents
`
`disclose systems that address these concerns, as they disclose systems that facilitate
`
`more efficient set up, maintenance, and operation. (’468 patent at 1:22-58).
`
`23. For example, the systems disclosed in the IPR patents contain
`
`computers that are programmed to prevent an infusion if the results of a strontium
`
`breakthrough test are greater than or equal to acceptable limits. (’468 patent at
`
`17:64-18:2.) The strontium breakthrough test occurs via a test sample that is located
`
`in a shielded well on-board the cart. (See Fig. 3B of the IPR patents.) An on-board
`
`dose calibrator may facilitate this process. (’468 patent at 18:56-19:4.)
`
`24.
`
`Independent claim 1 of the ’468 patent is directed to a mobile
`
`radioisotope generator system comprising, inter alia, “a movable platform carrying
`
`an infusion tubing circuit, an activity detector, a dose calibrator, a computer, and a
`
`shielding assembly containing a strontium/rubidium radioisotope generator …”
`
`(’468 patent at 23:60-24:21 (emphasis added).) Independent claim 24 also requires
`
`an on-board dose calibrator.
`
`25.
`
`Independent claim 21 of the ’468 patent requires, inter alia, a means
`
`for receiving activity data and controlling the mobile radioisotope generator system,
`
`wherein this means is configured “to receive breakthrough activity data from the
`
`means for receiving eluate and measuring breakthrough activity, determine at least
`
`13
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`an activity of strontium-82 and an activity of strontium-85 in the eluate from the
`
`breakthrough activity data, and prevent the patient infusion procedure if the activity
`
`of strontium-82 or the activity of strontium-85 exceeds an allowable limit.” Claim
`
`1 of the ’467 patent includes a similar limitation: “the computer is further configured
`
`to prevent a patient infusion procedure if a breakthrough test result exceeds an
`
`allowable limit.” Claim 13 of the ’467 patent includes a similar limitation:
`
`“preventing, with the computer, a patient infusion procedure if a breakthrough test
`
`result exceeds an allowable limit.” The combination of claims 1 and 2 of the ’468
`
`patent is similar: “… the computer being electronically coupled to the dose calibrator
`
`and configured to execute automated quality control testing using the dose calibrator
`
`… and the computer is further configured to prevent the patient infusion procedure
`
`if a quality control test result exceeds an allowable limit.” (’468 patent, claim 1.) …
`
`“… wherein the automated quality control testing comprises breakthrough testing.”
`
`(’468 patent, claim 2.) Claim 24 of the ’468 patent includes a similar limitation:
`
`“performing quality control testing on the eluate delivered to the dose calibrator,
`
`quality control testing including determining an activity of strontium-82 and an
`
`activity of strontium-85 in the eluate, and preventing, via a computer carried by the
`
`movable cart, a patient injection procedure if a quality control test result exceeds an
`
`allowable limit.” I note that the specification of the IPR Patents provides that
`
`14
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`“breakthrough testing” is strontium breakthrough testing. (’468 patent at 16:34-
`
`18:2; FIGS. 6 and 7A-7C.)
`
`26.
`
`I collectively refer to the limitations of the above paragraph as the
`
`“prevent limitations” as all require the computer to prevent a patient infusion
`
`procedure if the result of a strontium breakthrough test exceeds an allowable limit.
`
`VIII. POSITA
`27.
`I confirm that the definition of a person of ordinary skill in the art
`
`(“POSITA”) applied in my ITC Expert Report also applies to these IPRs. (Ex. 2011
`
`at ¶¶15-22). I have applied this definition in evaluating the claims of the IPR patents.
`
`Specifically, I have applied the following definition:
`
`A POSITA at the time of the inventions claimed in the IPR patents
`would generally have a graduate degree in medicine and/or in a medical
`related science, including physics, chemistry, biology, physiology,
`and/or biophysics, or a related field, and would generally have at least
`some clinical, research, and/or design experience with respect to PET
`imaging and/or PET imaging systems. An individual with an
`undergraduate degree along with significant experience could also be
`sufficiently skilled.
` The amount of experience following an
`undergraduate degree would depend on the level of formal education
`and amount of experience working with radiopharmaceuticals. Such a
`person may be working as part of a team.
`28.
`I understand Petitioner has proposed the following definition of a
`
`15
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`POSITA:
`
`“A person having ordinary skill in the art at the time of the alleged
`invention (“POSITA”) has a graduate’s degree with some emphasis in
`equipment design, automation, or controls, such as electrical
`engineering, systems engineering, mechanical engineering, or a related
`field, or an undergraduate degree in such fields with two to three years’
`work experience in radioactive protection systems or in medical device
`product, automation, or instrumentation design and development,
`including work with prototypes and finished commercial products.
`Such a person would have had a basic understanding, through education
`or experience, of general design control principles and processes and
`practices for partial or full automation of existing processes or test
`procedures.” (IPR2018-01448 Petition at 10; Ex. 1015-’468 at § IV, Ex.
`1015-’467 at § IV.)
`
`I disagree that this is the correct definition as it does not actually require familiarity
`
`with elution of radioactive isotopes, PET imaging, or even systems employing any
`
`form of radioactive substance. Petitioner’s definition also allows the consideration
`
`of any instrumentation design or medical device design background, while ignoring
`
`that one of ordinary skill in the art would be particularly hesitant to make any
`
`changes to a system involving radioactive materials when that system has serious
`
`design concerns specifically associated with the radioactivity.
`
`29. The POSITA definition I have employed is more appropriate because,
`
`16
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`for example, the IPR patents relate to medical devices using radioisotopes for
`
`medical PET imaging, so a POSITA’s focus should be in this area rather than general
`
`design control or automation principles. The definition I have employed is also more
`
`appropriate because it includes research and/or design experience with respect to
`
`PET imaging and/or PET imaging systems, noting that the amount of experience
`
`following an undergraduate degree would depend on the level of formal education
`
`and amount of experience working with radiopharmaceuticals, and whether such a
`
`person may be working as part of a team.
`
`IX. CLAIM CONSTRUCTION
`30.
`I understand that, for the present IPRs, the Board will construe claim
`
`terms according to their broadest reasonable construction in light of the specification
`
`of the patent in which they appear. I have applied the broadest reasonable
`
`construction of claim terms in my analysis of the IPR patents.
`
`31.
`
`I understand claim 21 of the ’468 patent recites:
`
`“21. A mobile radioisotope generator system comprising:
`
`a shielding assembly configured to contain a strontium/rubidium
`radioisotope generator that generates radioactive eluate via elution of
`an eluant and an infusion tubing circuit comprising an eluate tubing line
`configured to convey eluate from the strontium/rubidium radioisotope
`generator;
`
`17
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`
`means for measuring an activity of the eluate flowing through the eluate
`tubing line;
`
`means for receiving eluate from the eluate tubing line and measuring
`breakthrough activity of the eluate; and
`
`means for receiving activity data from the means for measuring the
`activity of the eluate and controlling the mobile radioisotope generator
`system based on the received activity data to deliver a dose of eluate to
`a patient during a patient infusion procedure, wherein the means for
`receiving activity data and controlling the mobile radioisotope
`generator system is further configured to receive breakthrough activity
`data from the means for receiving eluate and measuring breakthrough
`activity, determine at least an activity of strontium-82 and an activity
`of strontium-85 in the eluate from the breakthrough activity data, and
`prevent the patient infusion procedure if the activity of strontinum[sic]-
`821 or the activity of strontium-85 exceeds an allowable limit.” (’468
`patent at 25:53-26:10 (emphasis added).)
`
`Thus, claim 21 includes three following three means:
`
` A means for measuring an activity of the eluate flowing through the eluate
`
`tubing line;
`
`
`
` 1
`
` This is an obvious, unintended typographical error. I will not highlight it further
`
`below, and will use the correct spelling of strontium.
`
`18
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`
` A means for receiving eluate from the eluate tubing line and measuring
`
`breakthrough activity of the eluate; and
`
` A means for receiving activity data from the means for measuring the activity
`
`of the eluate and controlling the mobile radioisotope generator system based
`
`on the received activity data to deliver a dose of eluate to a patient during a
`
`patient infusion procedure.
`
`32. Regarding the first means-plus-function term, I understand Dr. Stone
`
`points to an activity detector in the specification as structure that performs the
`
`function of measuring an activity of the eluate flowing through the eluate tubing line.
`
`(Ex. 1015-’468 at ¶¶218-219.) I agree that the activity detector is one structure in
`
`the specification of the ’468 patent that can perform the claimed function.
`
`33. Regarding the second means-plus-function term, I understand Dr. Stone
`
`points to a dose calibrator in the specification as structure that performs the functions
`
`of receiving eluate from the eluate tubing line and measuring breakthrough activity
`
`of the eluate. (Ex. 1015-’468 at ¶225.) I agree that the dose calibrator is one
`
`structure in the specification of the ’468 patent that can perform the claimed
`
`functions.
`
`34. Regarding the third mean-plus-function term, I understand Dr. Stone
`
`points to a controller in the specification as structure that performs the functions of
`
`19
`
`
`
`Declaration of Norbert J. Pelc, Sc.D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`U.S. Patent Nos. 9,299,467 and 9,299,468
`
`measuring the activity of the eluate and controlling the mobile radioisotope
`
`generator system based on the received activity data to deliver a dose of eluate to a
`
`patient during a patient infusion procedure. (Ex. 1015-’468 at ¶¶233-234.) I agree
`
`that the controller is one structure in the specification of the ’468 patent that can
`
`perform the claimed functions. I further note that the ’468 patent’s computer may
`
`be connected to the controller, and that some functions in the ’468 patent may be
`
`due to the computer. (’468 patent at 3:28-29, 5:41-6:5, 6:43-46, 7:14-28, 13:13-24,
`
`13:44-14:15. 21:45-50.)
`
`35. Claim 21 also requires the third means to be configured to “prevent the
`
`patient infusion procedure if the activity of strontium-82 or the activity of strontium-
`
`85 exceeds an allowable limit.” As in the ITC proceedings, Petitioner argues in these
`
`IPRs that Klein’s computer meets this requirement. I describe in detail below why
`
`Klein’s computer does not “prevent the patient infusion procedure if the activity of
`
`strontium-82 or the activity of strontium-85 exceeds an allowable limit.”
`
`X. THE PRIOR ART
`36.
`I understand the following references have been cited by Petitioner in
`
`the IPRs in an effort to invalidate the claims:
`
` Ex. 1014: “Precise 82Rb Infusion System for Cardiac Perfusion
`Measurement Using 3D Positron Emission Tomography,” Ottawa-
`Carleton Institute for Electrical and Computer Engineering (Feb. 2005), or
`
`20
`
`
`
`Declaration of Norbert J. Pelc, Sc-D.
`Patent Owner Responses in IPRs 2018-01448, -01449, and -01450
`US. Patent Nos. 9,299,467 and 9,299,468
`
`“the Klein Thesis” or “Klein.”
`
`0 Ex. 1021: “Bracco CardioGen—82® Infusion System User’s Guide, Rev.
`
`07” (July 20, 2004) or “the Bracco Manual”
`
`0 Ex. 1022: US. Patent Application Publication No. 2011/0178359 or
`
`“Hirschman”
`
`0 Ex. 1023: US. Patent Application Publication No. 2008/0242915 or
`
`“Jackson”
`
`0 Ex. 1024: US. Patent Application Publication No. 2004/0260143 or
`
`“Reilly”
`
`0 Ex. 1025: US. Patent Application Publication No. 2008/0177126 or
`
`“Tate,,
`
`37.
`
`I understand Petitioner asserts the following grounds of invalidity in the
`
`IPRs:
`
`IPR Number at. no.
`
`Alleed Grounds of Invalidi
`
`2018—01448 (’468 pat.)
`
`Claims 1—2, 4, 6—7, 9—17, 24-25 and 28
`are obvious based on Klein, Reilly and
`Tate
`
`Claim 8 is obvious based on Klein,
`2018-01448 (’468 pat.)
`
`Reilly, Tate and the Bracco Manual
`Claims 18, 20 and 27 are obvious
`based on Klein, Reilly, Tate and
`Hirschman
`
`2018-01448 (’468 pat-)
`
`
`
`Klein, Reill , Tate and Jackson
`
`Claims 14, 6—7, 9—10, 12—16, and 18—
`
`20 are antici ated b Klein
`
`2018-01449 ’467 at.
`
`Claims 8 and 21 are obvious over
`
`Klein and Tate
`
`21
`
`
`
`Declaration of N
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