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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`___________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`______________
`JUBILANT DRAXIMAGE INC.,
`Petitioner,
`v.
`
`BRACCO DIAGNOSTICS INC.,
`Patent Owner.
`
`______________
`
`
`
`Case IPR2018-01448
`Patent 9,299,468
`
`______________
`Patent Owner’s Preliminary Response
`
`

`

`IPR2018-01448
`US Patent No. 9,299,468
`
`
`
`Patent Owner’s Preliminary Response
`
`C. 
`
`I. 
`II. 
`
`Table of Contents
`INTRODUCTION ....................................................................................... 1 
`PETITIONER’S ASSERTED LEVEL OF ORDINARY SKILL IN
`THE ART AND CLAIM CONSTRUCTION ........................................... 2 
`III.  FACTUAL BACKGROUND: THE CITED PRIOR ART AND
`PROSECUTION HISTORY OF THE ’468 PATENT ............................. 3 
`A. 
`Overview of Petitioner’s art and arguments ..................................... 4 
`B. 
`The art at issue in the Petition and during prosecution ................... 7 
`1.  The “Klein” references ............................................................... 8 
`2.  The “mobile platform” references ........................................... 18 
`3.  The “printout” reference: the Bracco Manual (Ex. 1021) .... 20 
`4.  The “remote memory/computer” references.......................... 23 
`Overview of the art and arguments relied on by the examiner
`during prosecution ........................................................................... 24 
`1.  Prosecution of pertinent members of the ’468 patent family24 
`2.  Prosecution of the ’468 patent ................................................. 25 
`IV.  ARGUMENT ............................................................................................. 29 
`A. 
`Legal Standards ................................................................................ 29 
`B. 
`The Board should exercise its discretion and deny institution ...... 32 
`1.  Braun Factor 1: “the similarities and material differences
`between the asserted art and the prior art involved during
`examination” .................................................................................... 32 
`2.  Braun Factor 2: “the cumulative nature of the asserted art
`and the prior art evaluated during examination” ........................ 45 
`3.  Braun Factor 3: “the extent to which the asserted art was
`evaluated during examination” ...................................................... 50 
`4.  Braun Factor 4: “the extent of the overlap between the
`arguments made during examination and the manner in which a
`petitioner relies on the prior art or a patent owner distinguishes
`the prior art” .................................................................................... 52 
`5.  Braun Factor 5: “whether a petitioner has pointed out
`
`Page i of vii
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`Patent Owner’s Preliminary Response
`
`IPR2018-01448
`US Patent No. 9,299,468
`sufficiently how the Office erred in evaluating the asserted prior
`art” .................................................................................................... 63 
`6.  Braun Factor 6: “the extent to which additional evidence and
`facts presented in the petition warrant reconsideration of the
`prior art or arguments” .................................................................. 65 
`7.  Weighing the factors ................................................................. 65 
`V.  CONCLUSION .......................................................................................... 68 
`
`
`
`
`
`
`Page ii of vii
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`

`

`IPR2018-01448
`US Patent No. 9,299,468
`
`
`
`Patent Owner’s Preliminary Response
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Apotex Inc. v. Celgene Corp.,
`IPR2018-00685, Paper 8 (PTAB Sept. 27, 2018) ............................................... 67
`Becton Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (PTAB Dec. 15, 2017) ........................................passim
`Boehringer Ingelheim Int’l GMBH v. Biogen, Inc.,
`IPR2015-00418, Paper 14 (PTAB Jul. 13, 2015) ............................................... 21
`Cultec, Inc. v. StormTech LLC,
`IPR2017-00777, Paper 7 (PTAB Aug. 22, 2017) ............................................... 30
`In re Hall,
`781 F.2d 897-99 (Fed. Cir. 1986) ....................................................................... 20
`Harmonic Inc. v. Avid Tech., Inc.,
`815 F.3d 1356 (Fed. Cir. 2016) .......................................................................... 29
`Hospira, Inc. v. Genentech, Inc.,
`IPR2017-00739, Paper 16 (PTAB July 27, 2017) .............................................. 30
`Kyocera Wireless Corp. v. ITC,
`545 F.3d 1340 (Fed. Cir. 2008) .......................................................................... 21
`In re Magnum Oil Tools Int’l, Ltd.,
`829 F.3d 1364 (Fed. Cir. 2016) .......................................................................... 20
`Microsoft Corp. v. Corel Software, LLC,
`IPR2016-01300, Paper 13 (PTAB Jan. 4, 2017) ................................................ 21
`Mylan Pharm. v. Boehringer Ingelheim GMBH,
`IPR2016-01565, Paper 23 (PTAB Aug. 1, 2017) ............................................... 21
`NHK Spring Co., Ltd. v. Intri-Plex Techs., Inc.,
`IPR2018-00752, Paper 8 (PTAB Sept. 12, 2018) ............................................... 62
`Pfizer Inc. v. Giogen Inc.,
`IPR2017-01166, Paper 9 (PTAB Nov. 13, 2017) ............................................... 21
`
`Page iii of vii
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`Patent Owner’s Preliminary Response
`
`IPR2018-01448
`US Patent No. 9,299,468
`SAS Institute v. Iancu,
`138 S.Ct. 1348 (2018) ......................................................................................... 29
`Unified Patents Inc. v. Berman,
`IPR2016-01571, Paper 10 (PTAB Dec. 14, 2016) ....................................... 63, 67
`Statutes
`35 U.S.C. § 102 .......................................................................................................... 9
`35 U.S.C. § 102(b) ................................................................................................... 20
`35 U.S.C. §103 ........................................................................................................... 1
`35 U.S.C. § 314(a) & 325(d) .................................................................................... 29
`35 U.S.C. § 325(d) ............................................................................................passim
`
`
`
`Page iv of vii
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`

`IPR2018-01448
`US Patent No. 9,299,468
`
`
`
`Patent Owner’s Preliminary Response
`
`EXHIBIT LIST
`
`Exhibit
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`1006
`1007
`1008
`1009
`1010
`1011
`
`1012
`
`1013
`
`1014
`1015
`
`Description
`Petitioner’s Exhibits
`U.S. Patent No. 9,299,468
`Complaint, Bracco Diagnostics Inc. v. Jubilant DraxImage Inc.,
`Case No. 3-18-cv-04422 (D.N.J.)
`Complaint, In the Matter of Certain Strontium-Rubidium
`Radioisotope Infusion Systems, and Components Thereof
`Including Generators, Inv. No. 337-TA 3303 (U.S. I.T.C.)
`Order Granting Joint Motion to Stay Pending Resolution of ITC
`Proceedings (D.I. 9) Case No. 3-18-cv-04422 (D.N.J.)
`Waiver of Service, Bracco Diagnostics Inc. v. Jubilant
`DraxImage Inc.
`Prosecution History, U.S. application s.n. 12/137,356
`Prosecution History, U.S. application s.n. 12/137,377
`Prosecution History, U.S. application s.n. 12/137,363
`Prosecution History, U.S. application s.n. 12/137,364
`Prosecution History, U.S. application s.n. 12/808,467
`Prosecution History, U.S. application s.n. 14/455,631
`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) (“Alvarez-Diez”)
`Klein et al, “Precision Control of Eluted Activity from a Sr/Rb
`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) (“Klein-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) (“Klein Thesis”)
`Declaration of Robert T. Stone, Ph.D.
`
`Page v of vii
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`

`

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`
`Patent Owner’s Preliminary Response
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`IPR2018-01448
`US Patent No. 9,299,468
`1016
`Curriculum Vitae of Robert T. Stone, Ph.D.
`1017
`Declaration of Ventakesh Murthy, M.D.
`1018
`Barker, et al., U.S. Patent 4,585,009, granted April 29, 1986
`1019
`U.S. Pharmacopeia 23 National Formulary 18 (1995)
`1020
`Declaration of Andy Adler, Ph.D. with Attachments A-C
`Bracco CardioGen-82® Infusion System User’s Guide, Rev. 07
`(July 20, 2004)
`Hirschman, et al., U.S. Patent Publication No. 2011/0178359,
`filed December 28, 2007 (“Hirschman”)
`Jackson, et al., U.S. Patent Publication No. 2008/0242915, filed
`March 2, 2004 and published October 2, 2008 (“Jackson”)
`Reilly, et al., U.S. Patent Publication No. 2004/0260143,
`published December 23, 2004 (“Reilly”)
`Tate, et al., U.S. Patent Publication No. 2008/0177126, filed
`October 31, 2007 and published July 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. 1-7 (Sept. 11, 2015)
`Bracco CardioGen-82® Rubidium Rb 82 Generator, Rev. 43-
`8200 (May 2000)
`ISO 13485:2003 – Medical Devices – Quality Management
`Systems – Requirements for Regulatory Purposes (July, 2003)
`21 CFR Part 820.1 (2005)
`EN 62274:2005 – Medical Electrical Equipment – Safety of
`Radiotherapy Record and Verify Systems (December 28, 2005)
`21 CFR Part 11.1 (2004)
`10 CFR Part 20 (10 CFR 20.1001-2)
`10 CFR Part 20 (10 CFR 20.1003)
`The Chemical Rubber Co., Handbook of Radioactive Nuclides,
`Yen Wang ed., 1969
`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)
`
`1030
`1031
`1032
`1033
`
`1026
`
`1027
`
`1028
`1029
`
`1034
`
`1035
`
`Page vi of vii
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`

`
`
`Patent Owner’s Preliminary Response
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`1036
`
`1037
`
`1038
`
`IPR2018-01448
`US Patent No. 9,299,468
`Bates et al. “The impact of computerized physician order entry
`on medication error prevention,” J Am Med Inform Assoc.
`1999;6(4):313–321
`Defense Information Systems Agency – Medical Devices
`Security Technical Implementation Guide, version 1, release 1,
`27 July 2010
`HIMSS, “Implementation Guide for the Use of Bar Code
`Technology in Healthcare” (2003)
`Complainant Bracco Diagnostics Inc.’s Responses to
`Respondent’s Fourth Set of Interrogatories (No. 68), In the
`Matter of Certain Strontium-Rubidium Radioisotope Infusion
`Systems, and Components Thereof Including Generators, Inv.
`No. 337-TA 3303 (U.S. I.T.C.)
`deKemp, U.S. Patent Publication No. 2007/0213848 (“deKemp-
`848”)
`deKemp, U.S. Patent Publication No. 2007/0140958
`Declaration of Carol Wadke
`Patent Owner’s Exhibits
`U.S. Patent No. 6,767,319 (“Reilly-319”)
`Redline comparison between Ex. 1024 (Reilly) and Ex. 2001
`(Reilly-319) generated using Microsoft Word
`
`1040
`1041
`1042
`
`1039
`
`2001
`
`2002
`
`Page vii of vii
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`IPR2018-01448
`US Patent No. 9,299,468
`I.
`INTRODUCTION
`
`
`
`Patent Owner’s Preliminary Response
`
`Patent Owner Bracco Diagnostics Inc. (“Patent Owner”) submits the
`
`following Preliminary Response to the Petition for Inter Partes Review (the
`
`“Petition”) filed by Jubilant Draximage Inc. (“Petitioner”) regarding Claims 1-2, 4-
`
`19, and 24-28 (“the Challenged Claims”) of U.S. Patent No. 9,299,468 (“the ’468
`
`Patent”). (Petition at 1; 87.) Petitioner has alleged that the Challenged Claims are
`
`unpatentable under 35 U.S.C. §103 over several prior art references, using multiple
`
`grounds. (Id. at 24-26.) For the below reasons, the Board should deny Petitioner’s
`
`IPR request on all grounds.
`
`The ’468 patent relates to computer-facilitated systems and methods for
`
`maintaining and operating a radiopharmaceutical infusion system. (Ex. 1001 at
`
`1:23-58; Abstract.) Such systems and methods are used to generate and infuse
`
`radiopharmaceuticals, such as rubidium-82, into patients for the purpose of positron
`
`emission tomography (“PET”) imaging. (Id.) In particular, the Challenged Claims
`
`are directed to systems and methods for generating a rubidium radioactive eluate,
`
`using a computer to perform quality control tests with respect to the rubidium
`
`radioactive eluate, and infusing the rubidium radioactive eluate into the patient. (Id.
`
`at 23:60-27:3.) The claims further require quality control and safety features. (Id.)
`
`Petitioner seeks to invalidate the Challenged Claims on the basis of four
`
`invalidity grounds. (Petition at 26.) Each of these grounds is based on prior art that
`
`Page 1 of 69
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`IPR2018-01448
`US Patent No. 9,299,468
`the PTO previously considered during prosecution of the ’468 patent. Although
`
`Patent Owner’s Preliminary Response
`
`
`
`Petitioner contends its invalidity grounds are “new,” they are in fact merely
`
`cumulative of the art and arguments considered by the examiner during prosecution
`
`of the ’468 patent. Inter partes review under these circumstances—i.e.,
`
`readjudicating similar issues that were raised by the examiner and overcome by
`
`Patent Owner—wastes the Board’s and Patent Owner’s resources. Accordingly, the
`
`Board should exercise its discretion under 35 U.S.C. § 325(d) and deny institution
`
`of the Petition. Ground 2 also fails because Petitioner failed to present any
`
`evidence beyond a date listed on the cover page of the manual to support its
`
`contention that the Bracco Manual (Ex. 1021) qualifies as prior art.
`
`Thus, Patent Owner requests that the Board reject the Petition in its entirety,
`
`and decline to institute review.
`
`II.
`
`PETITIONER’S ASSERTED LEVEL OF ORDINARY SKILL IN THE
`ART AND CLAIM CONSTRUCTION
`
`For purposes of this Preliminary Response only, the level of ordinary skill in
`
`the art and Petitioner’s assertion that all claim terms have their ordinary and
`
`customary meaning are not pertinent to any of Patent Owner’s arguments herein.
`
`Further, Patent Owner expressly disagrees with Petitioner’s asserted level of
`
`ordinary skill, and reserves the right to provide its own definition of the level of
`
`ordinary skill in the art, should the Board institute review. Patent Owner also
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`IPR2018-01448
`US Patent No. 9,299,468
`reserves its right to submit any pertinent claim construction(s), should the Board
`
`Patent Owner’s Preliminary Response
`
`
`
`institute review.
`
`III. FACTUAL BACKGROUND: THE CITED PRIOR ART AND
`PROSECUTION HISTORY OF THE ’468 PATENT
`
`The Petition purports to set forth a “new question of patentability.” (Petition
`
`at 8-9.) Specifically, Petitioner argues that it presents new arguments even though
`
`it relies on prior art that the examiner already considered. (Id. at 8.) This argument
`
`relies on the contention that the Klein Thesis (Ex. 1014) “discloses the claim
`
`limitations that the Patent Office could not find in the prior art, and Klein was not
`
`substantively discussed during prosecution of the ’468 Patent,” as well as that the
`
`Klein Thesis “has far better disclosure than the references cited during
`
`prosecution.” (Petition at 8-9.) Petitioner never explains this contention, or
`
`supports it with evidence.
`
`Petitioner’s purportedly “new” argument is not new at all. It relies on the
`
`same or closely-related references that were previously applied by the examiner
`
`during prosecution. For example, the Klein Thesis is not “new” to the Office,
`
`because it considered by the examiner. Further, the Klein Thesis is merely a
`
`cumulative follow-on document that builds on prior work that was described in
`
`other references that were substantively considered by the examiner, including the
`
`Alvarez-Diez publication (Ex. 1012). It is also not “new” because the examiner
`
`considered similar publications that resulted from the underlying work described in
`
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`IPR2018-01448
`US Patent No. 9,299,468
`the Klein Thesis, including Klein-2004 (Ex. 1013). The Klein Thesis also provides
`
`Patent Owner’s Preliminary Response
`
`
`
`overlapping disclosures as compared to other Klein references that were analyzed
`
`by the examiner, including deKemp-848 (Ex. 1040). deKemp-848 names Klein as
`
`a co-inventor in addition to Klein’s thesis adviser, deKemp. All of these references
`
`were considered during prosecution and were often discussed at length. The
`
`Petition effectively ignores them.
`
`Below, Patent Owner provides a brief Overview of the Petition, the
`
`individual references that are relied on in the Petition, and the prosecution history.1
`
`A. Overview of Petitioner’s art and arguments
`
`The Petition sets forth four grounds of invalidity, each relying on at least
`
`three references:
`
`
`1 The descriptions in this Preliminary Response of the individual references that are
`
`relied on in the Petition are based at least in part on how those references are
`
`characterized in the Petition. Patent Owner notes, however, that it does not agree
`
`with all of the Petitioner’s characterizations of such references, and thus Petitioner
`
`specifically reserves the right to dispute such characterizations in the event the
`
`Board institutes review.
`
`Page 4 of 69
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`IPR2018-01448
`US Patent No. 9,299,468
`
`
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`Patent Owner’s Preliminary Response
`
`
`
`(Petition at 26.)
`
`The Petition primarily relies on the Klein Thesis for all four invalidity
`
`grounds. Below, Patent Owner identifies where, and for which limitations (using
`
`Petitioner’s numbering scheme), Petitioner relies on additional references:
`
`GROUND 1
`Claim 1
`[1.1] a movable platform carrying …
`[c] a dose calibrator,
`
`Claim 9
`[9] The system of claim 1, wherein the dose calibrator
`is at least one of integrated into the shielding assembly
`or contained within a well of the shielding assembly.
`
`Ex. 1014-Klein
`Ex. 1024-Reilly
`Ex. 1025-Tate
`
`(Petition at 33-35)
`
`Ex. 1014-Klein
`Ex. 1024-Reilly
`Ex. 1025-Tate
`
`(Petition at 50-53)
`
`Claim 16
`[16] The system of claim 1, wherein the movable Ex. 1014-Klein
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`US Patent No. 9,299,468
`platform rests on wheels configured to roll and swivel. Ex. 1025-Tate
`
`(Petition at 59-60)
`
`
`
`Patent Owner’s Preliminary Response
`
`Claim 24
`[24.3] delivering a portion of eluate via the tubing line
`to a dose calibrator carried by the movable cart,
`
`GROUND 2
`Claim 8
`[8] The system of claim 1, wherein the movable
`platform further carries a printer configured to provide
`a printout of quality control test information.
`
`GROUND 3
`Claim 18
`[18] The system of claim 17, further comprising an
`encoded
`information reader configured
`to read
`encoded information from at least one of the eluant
`reservoir,
`the
`infusion
`tubing circuit, and
`the
`strontium/rubidium
`radioisotope
`generator,
`and
`wherein the computer is further configured to receive
`information read from a label attached to the at least
`one of the eluant reservoir, the infusion tubing circuit,
`and the strontium/rubidium radioisotope generator.
`Claim 20
`[20] The system of claim 1, wherein the computer is
`configured to connect to a removable computer
`readable storage device and transfer quality control
`information to the removable computer readable
`storage device.
`
`Claim 27
`[27] The method of claim 25, further comprising
`transferring, via the computer carried by the movable
`cart, quality control information to a removable
`computer readable storage device.
`
`GROUND 4
`Claim 5
`
`Page 6 of 69
`
`Ex. 1014-Klein
`Ex. 1024-Reilly
`Ex. 1025-Tate
`
`(Petition at 65-68)
`
`Ex. 1014-Klein
`Ex. 1021-Bracco
`
`(Petition at 75-76)
`
`Ex. 1022-Hirschman
`
`(Petition at 80)
`
`Ex. 1022-Hirschman
`
`(Petition at 81)
`
`Ex. 1022-Hirschman
`
`(Petition at 81)
`
`

`

`IPR2018-01448
`US Patent No. 9,299,468
`[5] The system of claim 1, wherein the computer is
`configured to automatically transfer quality control
`test information to one or more remote computers.
`
`
`
`Patent Owner’s Preliminary Response
`
`Ex. 1022-Hirschman
`Ex. 1023-Jackson
`
`(Petition at 85-87)
`
`Ex. 1022-Hirschman
`Ex. 1023-Jackson
`
`(Petition at 85-87)
`
`Claim 26
`[26] The method of claim 25, further comprising
`transmitting, via the computer carried by the movable
`cart, quality control information to one or more remote
`computers.
`
`The table above illustrates that Petitioner relies on the Tate/Reilly references
`
`in Ground 1 for disclosures relating to a movable platform that carries a dose
`
`calibrator. Petitioner relies on the Bracco Manual reference in Ground 2 for
`
`disclosures relating to a “printout” requirement. The Hirschman reference is relied
`
`on in Ground 3 for disclosures relating to reading encoded information and
`
`removable storage. Finally, the Hirschman and Jackson references are relied on in
`
`Ground 4 for disclosures relating to remote computers.
`
`B.
`
`The art at issue in the Petition and during prosecution
`
`Petitioner admits that “the Office considered the references relied upon in
`
`this Petition during original prosecution[.]” (Petition at 8.) Nonetheless, Petitioner
`
`argues that it is presenting a new question of patentability on the basis that the Klein
`
`Thesis was not substantively discussed during prosecution. However, as shown
`
`below, the Klein Thesis, for all intents and purposes, was analyzed during
`
`prosecution because the Office has already considered and substantively analyzed
`
`several references that are directly related to the work described in the Klein Thesis.
`
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`IPR2018-01448
`US Patent No. 9,299,468
`As further shown below, the secondary references that Petitioner relies on
`
`Patent Owner’s Preliminary Response
`
`
`
`were also analyzed by the examiner, or are cumulative of the Hirschman reference.
`
`Hirschman was heavily cited during prosecution, so Petitioner’s secondary
`
`references are merely cumulative of the art analyzed by the examiner.
`
`1.
`
`The “Klein” references
`
`The Klein Thesis is the primary reference cited by Petitioner. (Petition at 8-
`
`9.) In this section, Patent Owner provides a brief summary of the Klein Thesis and
`
`several closely-related publications that either name Ran Klein as an author or
`
`inventor, or provided the foundation for his thesis work.
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`IPR2018-01448
`US Patent No. 9,299,468
`a)
`
`
`
`Patent Owner’s Preliminary Response
`
`Klein Thesis (Ex. 1014)2
`
`The Klein Thesis is a graduate thesis submitted based on Ran Klein’s work
`
`with the University of Ottawa Heart Institute (“UOHI”). Dr. Klein is the author
`
`identified on the cover page of the thesis, and Dr. Klein credits his advisors Robert
`
`deKemp and Andy Adler for their support with the project. (Ex. 1014-Klein at ii.)
`
`As Dr. Klein explains, his thesis describes the development of a Rubidium-
`
`82 infusion system for use in positron emission tomography (“PET”). (Id. at 1.)
`
`The infusion system described in the Klein Thesis built upon a system that was
`
`previously developed at UOHI:
`
`
`2 The Klein Thesis includes a February 2005 date on its face. Petitioner attempts to
`
`show that the Klein Thesis was published and publicly accessible to those of
`
`ordinary skill in the art by at least January 26, 2007. (Petition at 16-17.) In support
`
`of this assertion, Petitioner references a declaration of Andy Adler, one of Dr.
`
`Klein’s thesis advisors, and the Wayback Machine. (Id.) For purposes of this
`
`Preliminary Response only and without waiving its right to challenge the prior art
`
`status of the Klein Thesis in the future, Patent Owner does not currently address
`
`whether the Klein Thesis is prior art under 35 U.S.C. § 102. Patent Owner,
`
`however, reserves the right to do so in the future.
`
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`IPR2018-01448
`US Patent No. 9,299,468
`“The first generation 82Rb elution system developed at the UOHI
`was described by Alvarez-Diez et al., 1999 [30].” (Ex. 1014-Klein
`at 16 (emphasis added).)
`
`Patent Owner’s Preliminary Response
`
`The Alvarez-Diez publication (Ex. 1012) referenced in the quote above is described
`
`below in §III.B.1.c. The Klein Thesis explains:
`
`“[The Alvarez-Diez system] was based on an industrial PC running
`MS-DOS coupled to a LCD touch-screen. The software ensured
`that the daily protocol (discussed below) is followed and generated a
`recording of each elution. In addition, some rudimentary error
`detection was included. The system contained all the necessary
`components in a single cart, but had to be calibrated manually at a
`single flow rate … by monitoring an external dose calibrator during
`the calibration run.” (Id. at 17.)
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`The Klein Thesis describes a system that has the same functionality and is based on
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`the same hardware design as the Alvarez-Diez system:
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`“The RbES had to ensure the same functionality as the first
`generation system, while adding constant-activity elution capability,
`improved user interface, and additional automation to reduce
`radiation exposure to the operator and patients. The system was
`based on the hardware design of the first generation system but had
`an updated computer system, user interface, and operating system
`which enabled more advanced developments.” (Id.)
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`Thus, the Klein Thesis describes a system that is closely-related to the first-
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`generation Alvarez-Diez system.
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`The Klein Thesis also is not a standalone publication. In addition to its close
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`Patent Owner’s Preliminary Response
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`relationship to the Alvarez-Diez system, the Klein Thesis resulted in additional
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`publications authored by Ran Klein and others at UOHI, including deKemp and
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`Adler. As of the February 2005 date listed on the Klein Thesis, the underlying
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`work had already resulted in at least three additional publications:
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`
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`(Ex. 1014-Klein at 3.) The first bullet references the Klein-2004 publication that is
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`in the IPR record as Ex. 1013.
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`The Petition relies on the Klein Thesis for the vast majority of the claim
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`limitations at issue in each of the four grounds. The Klein Thesis was in the
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`prosecution record for the priority applications (see, e.g., Exs. 1007 at 394, 411;
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`1009 at 708, 818; and 1010 at 582, 847). It was also considered by the examiner
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`during the prosecution of the ’468 patent itself (Ex. 1011 at 213, 366). Although
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`the thesis itself was not directly discussed at length during prosecution, the
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`prosecution histories reveal a repeated reliance on related Klein publications,
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`Patent Owner’s Preliminary Response
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`including Klein-2004, Alvarez-Diez, and deKemp-848.
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`b)
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`Klein-2004 (Ex. 1013)
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`One of the references that manifested from Ran Klein’s thesis work is the
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`Klein-2004 reference entitled “Precision Control of Eluted Activity from a Sr/Rb
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`Generator for Cardiac Positron Emission Tomography.” (Ex. 1013-Klein at 1.)
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`The Klein-2004 reference lists Dr. Klein as the lead author, followed by Dr. Klein’s
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`two thesis advisers (Adler and deKemp) and R.S. Beanlands.
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`The Klein-2004 reference was considered during prosecution of the ’468
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`patent’s parent applications (see, e.g., Ex. 1007 at 138, 252; Ex. 1009 at 494, 559;
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`Ex. 1010 at 578, 723), and was also substantively analyzed during prosecution of
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`the ’468 patent. (Ex. 1011 at 87-91 and 115-30.)
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`Klein-2004 includes a Rubidium-82 elution system diagram:
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`The figure above depicts a system diagram that is nearly identical to the hardware
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`design illustrated in Figure 2-2 of the Klein Thesis:
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`(Ex. 1014-Klein at 19.)
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`In Petitioner’s argument
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`regarding a purported “new question of
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`patentability” (Petition at 8-9), Petitioner’s only statement regarding differences
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`between the Klein Thesis and Klein-2004 is the following:
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`“Although Klein-2, deKemp ’848 and deKemp ’958 refer to
`undesirable effects of strontium breakthrough, none discloses a
`computer to test for such issues or to implement safety protocols
`when detected. (Ex. 1013, 1040, 1041).” (Petition at 9.)
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`Significantly, Petitioner does not present any specific citations to Klein-2004 to
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`support this statement. Indeed, the statement appears to be inconsistent with Klein-
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`2004, which presents similar disclosures to those relied on in the Klein Thesis.
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`(Compare Ex. 1014-Klein at 3 & FIG. 2-2 with Ex. 1013-Klein at FIG. 1 (including
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`a “Computer” and reference to “control signals”).)
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`c)
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`Patent Owner’s Preliminary Response
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`Alvarez-Diez (Ex. 1012)
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`The Alvarez-Diez reference names Teresa Alvarez-Diez as the lead author
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`and also lists deKemp as a co-author. (Ex. 1012-Alvarez-Diez at 1015.) As noted
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`above, the Klein Thesis explains that this reference describes a predecessor system
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`at the UOHI. (Ex. 1014-Klein at 16-17.) Further, the Klein Thesis system was
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`based on the same hardware described in Alvarez-Diez. (Id.)
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`Alvarez-Diez is analyzed at length in the prosecution history of the ’468
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`patent. (See, e.g., Ex. 1011 at 56-61, 79-82, 87-91, 115-30.) Alvarez-Diez depicts
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`an automated patient delivery system (D) that is connected to a controlling
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`computer with a touch screen (C) on a stainless steel cart (G):
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`(Ex. 1012-Alvarez-Deiz at 1020.)
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`In Petitioner’s argument
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`regarding a purported “new question of
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`patentability” (Petition at 8-9), Petitioner’s only statement regarding differences
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`between the Klein Thesis and Alvarez-Diez is the following:
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`“Alvarez-Diez describes that a generator is connected to a delivery
`system only after initial quality control is finalized. Ex [sic] 1012,
`at 1020.” (Petition at 9 (emphasis in Petition).)
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`Petitioner’s citation to 1020 appears to refer to the following statement in Alvarez-
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`Diez:
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`“When the initial quality control of the 82Sr/82Rb generator is
`finalized, the generator is connected to an automated delivery
`system (Fig. 5).” (Ex. 1012-Alvarez-Diez at 1020.)
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`Patent Owner’s Preliminary Response
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`Petitioner does not explain this excerpt in any way. Petitioner also does not explain
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`how such a distinction is material in view of the Challenged Claims, given that it
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`appears to refer to connecting a patient to a generator (see caption text for Figure 5,
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`reproduced above). Petitioner further ignores that these passages relate to initial
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`quality control, which differs from the discussion of quality control itself. (See,
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`e.g., Ex. 1012-Alvarez-Diez at §2.4.) Accordingly, Petitioner has provided no
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`explanation for what additional disclosure in the Klein Thesis renders its argument
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`“new,” in view of the lengthy discussion of Alvarez-Diez during prosecution.
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`d)
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`deKemp-848 (Ex. 1040)
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`deKemp-848 is a published patent application that lists Robert deKemp and
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`Ran Klein as inventors. This reference was also relied on by the examiner during
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`prosecution of the ’468 patent. (See, e.g., Ex. 1011 at 146-52, 172-86.) deKemp-
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`848 was also analyzed in detail during prosecution of the parent applications. (See,
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`e.g., Ex. 1010 at 176-83, 193, 197-217, 250-57, 271-89, 309-17, 330-47, 386-89,
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`401-18, 483-89, 551-67, 838-45, 857-69, 907-15, 929-47.)
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`deKemp-848 depicts a similar elution system diagram to those shown above:
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`(Ex. 1040-deKemp-848 at FIG. 3.)
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`In Petitioner’s argument
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`regarding a purported “new question of
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`patentability” (Petition at 8-9), Petitioner’s only statement regarding differences
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`between the Klein Thesis and the deKemp references is the following:
`
`“Although Klein-2, deKemp ’848 and deKemp ’958 refer to
`undesirable effects of strontium breakthrough, none discloses a
`computer to test for such issues or to implement safety protocols
`when detected. (Ex. 1013, 1040, 1041).” (Petition at 9.)
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`Petitioner does not present any specific citations to deKemp-848 to support this
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`statement. Indeed, Petitioner’s characterization again appea