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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 IPR2018-01449
`Patent 9,229,467
`
`______________
`
`Patent Owner Response
`
`
`
`IPR2018-01449
`U.S. Patent No. 9,299,467
`
`
`
`Patent Owner Response
`
`Contents
`
`I.
`II.
`
`INTRODUCTION .......................................................................................... 1
`PRELIMINARY ITEMS ............................................................................... 2
`A.
`Related Proceedings ............................................................................. 2
`B.
`Claim Construction .............................................................................. 3
`C.
`POSITA Definition .............................................................................. 3
`III. TECHNOLOGICAL BACKGROUND AND OVERVIEW OF THE ’467
`PATENT ......................................................................................................... 5
`IV. KLEIN’S COMPUTER DOES NOT PREVENT PATIENT INFUSIONS
`IF A BREAKTHROUGH TEST RESULT EXCEEDS AN ALLOWABLE
`LIMIT ............................................................................................................. 8
`A.
`Petitioner’s arguments are the same across all three IPRs .................. 9
`B.
`Klein does not disclose a computer that prevents a patient infusion
`procedure if a strontium breakthrough test result exceeds an
`allowable limit ...................................................................................12
`THE BRACCO MANUAL ..........................................................................19
`V.
`VI. DR. MURTHY’S TESTIMONY LACKS FOUNDATION ........................20
`VII. CONCLUSION ............................................................................................21
`
`
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`Page i of iii
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`TABLE OF AUTHORITIES
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`
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`Patent Owner Response
`
` Page(s)
`
`Cases
`Cordis Corp. v. Boston Scientific Corp.,
`561 F.3d 1319 (Fed. Cir. 2009) .......................................................................... 19
`In re Magnum Oil Tools,
`829 F.3d 1364 (Fed. Cir. 2016) .......................................................................... 19
`Nuna Baby Essentials, Inc. v. Britax Child Safety, Inc.,
`IPR2018-01683, Paper 11 (PTAB Dec. 18, 2018) ............................................. 21
`Pregis Corp. v. Kappos,
`700 F.3d 1348 (Fed. Cir. 2012) .......................................................................... 12
`In re Robertson,
`169 F.3d 743 (Fed. Cir. 1999) ............................................................................ 18
`Transocean Offshore Deepwater Drilling, Inc. v. Maersk Contractors
`USA, Inc.,
`617 F.3d 1296 (Fed. Cir. 2010) .......................................................................... 12
`Verdegaal Bros., Inc. v. Union Oil Co. of California,
`814 F.2d 628 (Fed. Cir. 1987) ............................................................................ 13
`Other Authorities
`37 C.F.R. § 42.64 ..................................................................................................... 20
`37 C.F.R. § 42.5(c)(3) .............................................................................................. 21
`
`
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`Page ii of iii
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`IPR2018-01449
`U.S. Patent No. 9,299,467
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`Patent Owner Response
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`EXHIBIT LIST
`
`2007
`
`2008
`
`2009
`
`Description
`Exhibit
`2001 U.S. Patent Application Publication No. 2011/0178359, filed December
`28, 2007
`[RESERVED]
`2002
`2003 Declaration of Dr. Norbert Pelc
`ITC Deposition of Dr. Robert Stone, October 9, 2018 (Redacted)
`2004
`ITC Deposition of Dr. Robert Stone, October 10, 2018 (Redacted)
`2005
`ITC Trial Testimony of Dr. Robert Stone, April 15, 2019 (Public
`2006
`Version)
`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
`2010 Deposition testimony of Dr. Robert Stone in IPRs 2018-01448, -01449,
`and -01450
`ITC Corrected 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
`2014 CAPINTEC CRC-15R User Manual, Nov. 2004
`2015 CAPINTEC CRC-15R User Manual, July 2007
`2016 Deposition testimony of Dr. Venkatesh Murthy in IPRs 2018-01448,
`-01449, and -01450
`Exhibit 1001 from Dr. Murthy’s Deposition (corrections to Ex. 1017)
`
`2017
`
`
`
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`Page iii of iii
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`INTRODUCTION
`I.
`Patent Owner Bracco Diagnostics Inc. (“Patent Owner”) submits the
`
`Patent Owner Response
`
`
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`following Patent Owner Response (“POR”) to the Institution Decision of February
`
`8, 2019 (“Decision”) and the Petition of August 22, 2018 (“Petition”). The Petition
`
`requested cancellation of claims 1-4, 6-16, and 18-22 (the “Challenged Claims”) of
`
`U.S. Patent No. 9,299,467 (“the ’467 patent”) based on three grounds, all of which
`
`require a finding that the primary reference of Klein (Ex. 1014) discloses a computer
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`“configured to prevent a patient infusion procedure if a breakthrough test result
`
`exceeds an allowable limit” (claim 1) or that prevents “a patient infusion procedure
`
`if a breakthrough test result exceeds an allowable limit” (claim 13). The Decision
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`instituted trial after finding that Petitioner had established a likelihood of prevailing
`
`with respect to at least one challenged claims. (Decision at 13.) The evidence now
`
`of record compels a different conclusion.
`
`Klein does not disclose a computer that prevents patient infusion procedures
`
`based on the results of breakthrough testing. While Klein has a computer, and
`
`Klein’s computer does communicate with the dose calibrator, Klein’s computer does
`
`not prevent patient infusion procedures if a strontium breakthrough test result
`
`exceeds an allowable limit. Rather, the decision whether to go forward with patient
`
`infusions is left up to the operator, as explained below.
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`
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`Page 1 of 22
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`PRELIMINARY ITEMS
`II.
`A. Related Proceedings
`Related Patent No. 9,229,468 (“the ’468 patent”) is the subject of two
`
`Patent Owner Response
`
`concurrent IPRs filed by Petitioner (IPR2018-01448 and -01450). Concurrent Patent
`
`Owner Responses are being filed in those cases.
`
`Both the ’467 and the ’468 patents are the subject of District Court litigation
`
`between Bracco Diagnostics Inc. v. Jubilant DraxImage Inc., Case No. 3-18-cv-
`
`04422 (D.N.J.), which is stayed pending resolution of an Investigation by the U.S.
`
`International Trade Commission (337-TA 3303 (U.S. I.T.C.) “ITC”) involving
`
`related patents. (Exs. 1002-1004.) The District Court case would be affected by a
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`decision in this inter partes review.
`
`Further, an ITC evidentiary hearing was held April 11-17 relative to the
`
`related patents, and many of the same factual issues disputed there are also in dispute
`
`here. Accordingly, Patent Owner includes the pertinent testimony of Dr. Stone
`
`(Petitioner’s expert) and Dr. Pelc (Patent Owner’s expert) herewith. (Exs. 2004-
`
`2007; 2011-2013).
`
`Additionally, during his deposition in these IPRs, Dr. Stone confirmed the
`
`accuracy of his prior ITC testimony. (Ex. 2010 at 7:18-9:4 and 13:21-15:8 for Exs.
`
`2004-2005 and 15:9-19:9 for Exs. 2006-2007; see also Ex. 2010 at 73:21-77:10,
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`84:12-85:18, 91:1-92:19, 95:4-21, 100:14-103:4, 108:3-117:17.) Given the sworn
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`Page 2 of 22
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`testimony of Dr. Stone in the ITC proceedings and that it was confirmed by Dr. Stone
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`Patent Owner Response
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`
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`in his deposition for this IPR, Patent Owner sometimes cites to the record of the ITC
`
`proceedings relative to facts pertinent to this proceeding (e.g., items associated with
`
`the disclosures of Klein and/or Tate). Patent Owner also sometimes cites to the ITC
`
`testimony of Dr. Pelc, who also confirmed his ITC testimony. (Ex. 2003-Pelc at
`
`¶¶12-16.)
`
`B. Claim Construction
`The present IPR was filed before the new IPR rules regarding claim
`
`construction were implemented. Accordingly, the Challenged Claims of the ’467
`
`patent are construed according to their broadest reasonable interpretation.
`
`Petitioner has not proposed any specific constructions and the Board did not
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`construe any claim terms in the Decision. (Petition at 12; Decision at 6-7.) Patent
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`Owner believes that no specific constructions are required at this time. However,
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`Patent Owner reserves the right to put forth any specific constructions in these
`
`proceedings, should the need arise.
`
`C. The definition of a POSITA
`As noted in the Petition, the parties disagree regarding the POSITA definition,
`
`both here and in the ITC. (Petition at 10-12.) Patent Owner continues to assert that
`
`a POSITA at the time of the invention claimed in the ’467 Patent would generally
`
`have a graduate degree in medicine and/or in a medical related science, including
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`Page 3 of 22
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`physics, chemistry, biology, physiology, and/or biophysics, and would generally
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`Patent Owner Response
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`
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`have at least some clinical, research and/or design experience with respect to PET
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`imaging and/or PET imaging systems. An individual with an undergraduate degree
`
`along with significant experience could also be sufficiently skilled. Further, the
`
`amount of experience following an undergraduate degree would depend on the level
`
`of formal education and amount of experience working with radiopharmaceuticals,
`
`and such a person may be working as part of a team. (Ex. 2003-Pelc at ¶27.)
`
`Patent Owner’s definition is proper because the ’467 patent relates to
`
`radioisotope devices for medical PET imaging, so one of ordinary skill in the art’s
`
`relevant experience should be in this area. Importantly, Petitioner’s proposed
`
`definition does not actually require familiarity with elution of radioactive isotopes,
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`PET imaging, or even systems employing any form of radioactive substance. As
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`such, Petitioner has attempted to open the door to considering any instrumentation
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`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
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`involving radioactive materials when that system has serious design concerns
`
`specifically associated with radioactivity. Patent Owner’s proposed definition is
`
`also proper because it includes research and/or design experience with respect to
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`PET imaging and/or PET imaging systems, noting that the amount of experience
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`following an undergraduate degree would depend on the level of formal education
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`Page 4 of 22
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`U.S. Patent No. 9,299,467
`and amount of experience working with radiopharmaceuticals, and whether such a
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`Patent Owner Response
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`
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`person may be working as part of a team. (Id. at ¶¶28-29.)
`
`Notwithstanding the discussion above, Petitioner has failed to show that the
`
`Challenged Claims are invalid under either party’s proposed level of skill.
`
`III. TECHNOLOGICAL BACKGROUND AND OVERVIEW OF THE ’467
`PATENT
`There are several tools for evaluating and/or diagnosing heart disease,
`
`including an electrocardiogram (EKG), an echocardiogram, a stress test, cardiac
`
`catheterization, cardiac computerized tomography (CT) scan, cardiac magnetic
`
`resonance imaging (MRI), and nuclear cardiology imaging. While cardiac
`
`catheterization is considered the “gold standard” for the diagnosis of coronary artery
`
`disease, nuclear cardiology imaging nevertheless has been the mainstay for
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`diagnosis and prognosis for decades because cardiac catheterization is invasive, not
`
`as widely available as nuclear cardiology imaging, and poses higher risk to the
`
`patient.
`
`One type of nuclear cardiology imaging is positron emission tomography or
`
`PET. As the ’467 patent describes:
`
`“Positron emission tomography (PET) is one type of diagnostic
`imaging, which utilizes doses of radiopharmaceuticals, for example,
`generated by elution within a radioisotope generator, that are injected,
`or infused into a patient. The infused dose of radiopharmaceutical is
`absorbed by cells of a target organ, of the patient, and emits radiation,
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`Page 5 of 22
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`Patent Owner Response
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`which is detected by a PET scanner, in order to generate an image of
`the organ.” (Ex. 1001 at 1:32-40; see also Klein at iii, Reilly at ¶0004,
`and Tate at ¶0003.)
`PET scanners for cardiology began to appear in or around the mid-1980’s. In
`
`1989, Bracco’s CardioGen-82 became the first FDA-approved radioimaging agent
`
`dedicated to cardiac PET, and it is available today for patients in need of cardiac
`
`PET exams, including patients in the United States. (Ex. 1026 at 1.)
`
`The ’467 patent discloses computer-facilitated maintenance and operation of
`
`systems that generate and infuse radiopharmaceuticals (e.g., rubidium-82) into
`
`patients for the purpose of PET imaging. The system 10 (pictured below) includes
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`shell 13, with a generator 21 located therein. (The generator 21 is not shown in FIG.
`
`1A, below, but is shown in FIG. 3A.)
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`Page 6 of 22
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`IPR2018-01449
`U.S. Patent No. 9,299,467
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`Patent Owner Response
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`
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`Generally, maintenance and operational procedures for radiopharmaceutical
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`generating and infusion systems may be complex, especially given safety and
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`efficacy concerns when handling radioisotopes. The ’467 patent discloses systems
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`that address these concerns, as it discloses systems that facilitate more efficient set
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`up, maintenance, and operation. (’467 patent at 1:23-56.)
`
`For example, the systems disclosed in the ’467 patent 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. (’467 patent at 17:56-61.) The
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`strontium breakthrough test occurs via a test sample that is located in a shielded well
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`Page 7 of 22
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`U.S. Patent No. 9,299,467
`on-board the cart. (See FIG. 3B of the ’467 patent.) An on-board dose calibrator
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`Patent Owner Response
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`
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`may facilitate this process. (’467 patent at 18:48-58.)
`
`IV. KLEIN’S COMPUTER DOES NOT PREVENT PATIENT INFUSIONS
`IF A STRONTIUM BREAKTHROUGH TEST RESULT EXCEEDS AN
`ALLOWABLE LIMIT
`Both independent claims of the ’467 patent require a computer that prevents
`
`a patient infusion procedure if a strontium breakthrough test result exceeds an
`
`allowable limit. Specifically, claim 1 requires “the computer is further configured
`
`to prevent a patient infusion procedure if a breakthrough test result exceeds an
`
`allowable limit.” (’467 patent at 23:62-64.) As explained relative to FIGS. 6 and
`
`7A-7C of the ’467 patent a “breakthrough test” is a strontium breakthrough test.
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`(’467 patent at 16:10-17:61.) Independent claim 13 requires “preventing, with the
`
`computer, a patient infusion procedure if a breakthrough test result exceeds an
`
`allowable limit.” (’467 patent at 24:43-44.) Klein fails to disclose these limitations.
`
`While Klein has a computer, and Klein’s computer does communicate with
`
`the dose calibrator, Klein’s computer does not prevent patient infusion procedures if
`
`a strontium breakthrough test exceeds an allowable limit. (Ex. 2003-Pelc at §XII;
`
`Ex. 2012 at 980:20-983:9.) The decision whether to prevent patient infusions is left
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`up to the operator. (Id.)
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`Page 8 of 22
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`Petitioner’s arguments are the same across all three IPRs
`A.
`Whether Klein discloses a computer that prevents a patient infusion procedure
`
`Patent Owner Response
`
`
`
`if a strontium breakthrough test result exceeds an allowable limit applies to all three
`
`IPRs filed by Petitioner, i.e., IPRs2018-01448, -01449, and -01450. Relative to the
`
`present IPR, claim 1 of the ’467 patent requires “the computer is further configured
`
`to prevent a patient infusion procedure if a breakthrough test result exceeds an
`
`allowable limit,” and claim 13 of the ’467 patent requires “preventing, with the
`
`computer, a patient infusion procedure if a breakthrough test result exceeds an
`
`allowable limit.” Claim 2 of the ’468 patent (challenged in IPR2018-01448) requires
`
`the computer to prevent the patient infusion procedure if a strontium breakthrough
`
`test result exceeds an allowable limit. Claim 21 of the ’468 patent (challenged in
`
`IPR2018-01450) requires “wherein the means for receiving activity data and
`
`controlling the mobile radioisotope generator system is further configured to …
`
`prevent the patient infusion procedure if the activity of strontium-82 or the activity
`
`of strontium-85 exceeds an allowable limit.” Claim 24 of the ’468 patent
`
`(challenged in IPR2018-01448) requires “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
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`preventing, via a computer carried by the movable cart, a patient injection procedure
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`Page 9 of 22
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`U.S. Patent No. 9,299,467
`if a quality control test result exceeds an allowable limit.” All of the above
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`Patent Owner Response
`
`
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`limitations are collectively hereinafter referred to as the “prevent limitations.”
`
`Petitioner’s arguments and evidence relative to the “prevent limitations” are
`
`the same across all of the IPRs. In IPR2018-01448 against the ’468 patent, Petitioner
`
`argues that Klein’s computer prevents patient infusion procedures due to strontium
`
`breakthrough testing by citing § XIII.C.8 of Dr. Stone’s Declaration and various
`
`quotes of Klein. (IPR2018-1448 Petition at 43-44.) In IPR2018-01450, also against
`
`the ’468 patent, Petitioner cites §XI.A.6 of the same Stone Declaration and the same
`
`Klein quotes. (IPR2018-1450 Petition at 41-42.)1 In related IPR 2018-01449
`
`against the ’467 patent, Petitioner cites §§ XI.A.7 (claim 1) and XI.J.5 (claim 13) of
`
`Dr. Stone’s ’467 Declaration and the same basic quotes of Klein. (IPR2018-01449
`
`Petition at 32-33 and 47-48.) Specifically, the Petitions cite the following passages
`
`of Klein:
`
`“The amount of Sr breakthrough activity must be strictly limited to the
`Health Canada guidelines.
` This issue is addressed by daily
`
`
`1 Patent Owner notes that the -01450 Petition does not have page numbers. As such,
`
`Patent Owner identifies page numbers by referring to the page of the PDF document
`
`itself, e.g., the “Introduction” begins on page 9 of 56 of the PDF and the conclusion
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`is on page 54 of 56 of the PDF.
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`Page 10 of 22
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`U.S. Patent No. 9,299,467
`breakthrough tests as part of the daily protocol ensured by the system.”
`(Klein at 33.)
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`
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`Patent Owner Response
`
`“Once the daily protocol has been completed successfully, patient
`elutions are enabled until the end of the day.” (Id. at 18.)
`
`“Daily calibration samples are used to test for the breakthrough of Sr
`activity; if significant Sr activity is detected, the generator cannot be
`used on humans.” (Id. at 122; see also id. at 16, 44.)
`
`“The system must ensure compliance with the daily protocol described
`in the previous chapter. A flush followed by a calibration run and
`successful breakthrough measurement must be completed in order to
`enable patient elutions for the remainder of the day. The system should
`delay at least 10 min between runs.” (Id. at 29.) (IPR2018-01449 only.)
`
`“The 82Rb infusion system software must ensure that the protocol is
`followed (i.e. that each run is enabled only after the prerequisites have
`been completed successfully).” (Id. at 44.) (IPRs2018-01449, -01450
`only.)
`
`“In addition it ensures that the daily protocol is followed, including a
`flush and calibration (including a test of breakthrough activity) at the
`start of each day.” (Id. at 55.) (IPRs2018-01449, -01450 only.)
`
`Dr. Stone cites these same disclosures. (Ex. 1015 at ¶¶157-166, 335-344; IPR2018-
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`01448/-01450 Ex. 1015 at ¶¶245-253; 361-371.) Thus, Petitioner’s arguments and
`
`evidence regarding the “prevent limitations” are the same across all three IPRs.
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`Page 11 of 22
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`B. Klein does not disclose a computer that prevents a patient infusion
`procedure if a strontium breakthrough test result exceeds an
`allowable limit
`What a reference discloses is a question of fact. Transocean Offshore
`
`Patent Owner Response
`
`Deepwater Drilling, Inc. v. Maersk Contractors USA, Inc., 617 F.3d 1296, 1303
`
`(Fed. Cir. 2010); Pregis Corp. v. Kappos, 700 F.3d 1348, 1353 (Fed. Cir. 2012).
`
`Petitioner argues that the independent claims of the ’467 patent are anticipated
`
`because Klein expressly discloses the prevent limitations. (Petition at 23, 32-33, 47-
`
`28.) The below quote from Dr. Stone’s Declaration is representative of Petitioner’s
`
`position:
`
`“This discussion [in Klein], in aggregate, discloses to a POSITA that
`Klein’s computer “prevent[s] a patient infusion procedure if a
`breakthrough test result exceeds an allowable limit.” As illustrated in
`FIG. 2-1, each day at midnight the system resets and the daily protocol,
`including breakthrough testing, must be completed before infusions are
`enabled again. As discussed, Klein’s computer manages all operations
`of the infusion system, including the pumps and valves which are
`operatively connected to the computer, allowing the computer software
`to prevent and enable infusions. By enabling infusions only after
`prerequisites are completed successfully, Klein discloses that the
`computer prevents patient infusions when breakthrough tests fail.
`Klein’s disclosure demonstrates to a POSITA that, if breakthrough
`testing indicates an abnormality, Klein’s computer will not permit the
`generator to be used on humans.” (IPR2018-01448/-01450 Ex. 1015 at
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`Page 12 of 22
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`
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`¶252 (emphasis added); see also ¶¶168, 370, and IPR2018-01449 Ex.
`1015 at ¶¶166, 248, 343.)
`
`
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`Patent Owner Response
`
`However, “a claim is anticipated only if each and every element as set forth in the
`
`claim is found, either expressly or inherently described, in a single prior art
`
`reference.” Verdegaal Bros., Inc. v. Union Oil Co. of California, 814 F.2d 628, 631
`
`(Fed. Cir. 1987).
`
`As the above testimony implicitly admits, nowhere does Klein ever expressly
`
`state that Klein’s computer prevents patient infusions if a strontium breakthrough
`
`test result exceeds an allowable limit. As shown, Dr. Stone’s conclusion focuses on
`
`pumps and valves, not the strontium breakthrough test result. None of the above
`
`cited portions of Klein expressly disclose a computer that prevents patient infusions
`
`based on a strontium breakthrough test result exceeding an allowable limit. Indeed,
`
`while Klein’s system does reset at midnight such that patient infusions are thereafter
`
`prohibited until the daily protocol is conducted, Klein’s computer does not determine
`
`whether to prevent patient infusions based on a strontium breakthrough test result
`
`exceeding an allowable limit. This decision is left to the operator. (Ex. 2003-Pelc
`
`at ¶¶95-96.)
`
`Klein describes how
`
`its computer facilitates
`
`testing for strontium
`
`breakthrough (Klein at 53-55), but nowhere does Klein disclose that the system’s
`
`computer prevents patient infusions if a strontium breakthrough test result exceeds
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`Page 13 of 22
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`an allowable limit. Indeed, Klein describes an experiment conducted to specifically
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`Patent Owner Response
`
`
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`observe excessive breakthrough and to study how it changes over time once it
`
`occurs. (Id. at 122.) Klein reports that they were able to continue eluting the
`
`generator for two more months. (Id.) If Klein’s computer were configured to
`
`prevent patient infusions based on strontium breakthrough test results, such an
`
`experiment would have been complicated or impossible. (Ex. 2003-Pelc at ¶97.)
`
`Nowhere does Klein state that the system prevented or attempted to prevent Rb82
`
`elution after high strontium breakthrough was observed or that they had to over-ride
`
`the computer or its software to be able to conduct the experiment. Because Klein’s
`
`system did not prevent this experiment, a POSITA would understand Klein as
`
`disclosing that the operator, not the computer, chooses whether to allow (or prevent)
`
`patient infusions if a strontium breakthrough test result exceeds an allowable limit.
`
`(Id.)
`
`Additionally, Klein specifically states:
`
`“The ability to accurately measure the breakthrough depends on the
`sensitivity of the dose calibrator…. If the eluted 82Rb activity is
`insufficient to accurately measure breakthrough, the automatic
`measurement is skipped. The operator may manually enter the
`breakthrough activity from a more sensitive instrument. (Klein at 52
`(emphasis added).)
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`Page 14 of 22
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`The operator may or may not conduct the measurement on a more sensitive
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`Patent Owner Response
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`
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`instrument, and the operator may or may not manually enter the breakthrough
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`activity. At this point, Klein’s computer has no certainty about the breakthrough
`
`results, yet Klein does not clearly state that the system is now locked out. Further,
`
`Klein includes numerous error messages, none of which are “breakthrough is too
`
`high, the system is locked out,” or something similar. (See e.g. id. at §3.5, 54, 61,
`
`and FIG. 3-12.) Instead, Klein discloses that it is possible for the automatic
`
`measurement of breakthrough activity to fail, at which point the system has no
`
`knowledge about what the breakthrough is: the breakthrough could be within limits,
`
`or the breakthrough could be higher than allowed limits. Yet there is no disclosure
`
`in the Klein that the system is locked out. (Ex. 2003-Pelc at ¶¶98-99.) As Dr. Pelc
`
`stated at the ITC:
`
`“So I mentioned earlier that Klein has a discussion of the required
`sensitivity of the dose calibrator and problems that come up if the dose
`calibrator isn’t sensitive enough. That’s what’s being talked about here.
`
`***
`
`I’d like to -- the sentence that starts with, If the eluted rubidium activity.
`So he says, If the rubidium activity is insufficient to accurately measure
`breakthrough, the automatic measurement is skipped. Because he
`knows that the measurement of the breakthrough ratio will not be
`accurate.
`
`Page 15 of 22
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`To me, this says that he is envisioning the possibility that he isn’t even
`able to calculate an accurate breakthrough. How could one infer that
`he then locks the system out?
`
`Patent Owner Response
`
`He goes on to say, The operator may manually enter the breakthrough
`activity from a more sensitive instrument.
`
`To me, this falls way short of teaching a computer configured to not
`allow patient elutions if the breakthrough test is above some threshold.”
`(Ex. 2012 at 983:10-984:23.)
`
`
`
`That Klein’s computer does not prevent patient infusion procedures based on
`
`a strontium breakthrough test result exceeding an allowable limit is also confirmed
`
`by FIG. 3-15 of Klein (shown below), which shows the daily dose calibration
`
`procedure used by Klein as part of the daily protocol. Based on this FIG. 3-15 and
`
`Klein’s related disclosures, Dr. Pelc explains:
`
`Page 16 of 22
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`
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`Patent Owner Response
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`
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`“So what Klein says is that you begin the day; you have
`to flush the generator and its lines; and then you have to
`perform a calibration run before you’re allowed to
`perform patient studies.
`
`And this is a flow chart in the Klein thesis about what does
`it mean -- what are the steps that you go through in order
`to conduct the calibration run.
`
`You see you initialize the system; you wait for the pump;
`you prime the lines; and then finally -- we’re about
`halfway down in the block diagram -- you start the
`elution.
`
`It’s got the step called cumulative time waiting. That
`means you’re waiting for the 60 seconds of the elution to
`complete. Then you switch some valves, and you push
`the saline into -- to flush all the fluid into the dose
`calibrator, as I mentioned earlier.
`
`And then it says ‘extra calibrator data.’ I’m not going to
`get into -- if you want, I can. But it’s -- the details of what
`that means. But that’s the initial measurement that Klein
`is making to calibrate the in-line detector. So that’s the
`first measurement that’s made.
`
`He then waits for the breakthrough reading. What that means is, the
`system is waiting for the 30 minutes and then acquiring data from the
`dose calibrator. There’s no question that the Klein computer is able to
`
`Page 17 of 22
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`directly, electronically receive data from the dose calibrator. It receives
`that data, and then it exits and terminates.
`
`
`
`Patent Owner Response
`
`I interpret this to say that a successful calibration run in Klein means
`you went through these steps. You flushed the generator. You flushed
`the lines. You -- there was no failure of the pump. There is no failure
`of the dose calibrator. The dose calibrator gave you numbers. And
`that’s what a successful run means. And if you do this, you can go on
`to do patient elutions.
`
`There’s nothing in the Klein thesis that says that based on the
`calculation of the breakthrough test, the computer prevents patient
`elutions. It does not say that.” (Ex. 2012 at 981:22-983:9 (emphasis
`added).)
`
`Thus, reading Klein as a whole, a POSITA would conclude it is the operator, not
`
`Klein’s computer, who decides whether to allow (or prevent) patient infusions if a
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`strontium breakthrough test result exceeds an allowable limit. (Ex. 2003-Pelc at
`
`¶¶100-101.)
`
`As noted above, Petitioner seems to be relying on an express anticipation
`
`argument. However, to the extent Petitioner is arguing inherent anticipation,
`
`Petitioner’s argument also fails because inherent anticipation cannot be established
`
`by a mere possibility of Klein’s computer preventing patient infusions based on a
`
`strontium breakthrough test result (as Petitioner seems to argue). In re Robertson,
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`169 F.3d 743, 745 (Fed. Cir. 1999). Indeed, as shown above, there is no such
`
`possibility.
`
`Page 18 of 22
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`
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`For at least these reasons, Petitioner has failed to show that Klein discloses
`
`Patent Owner Response
`
`
`
`the preventing limitations of the IPRs. Thus, Petitioner’s IPR challenges on this
`
`basis fail. In re Magnum Oil Tools, 829 F.3d 1364, 1376 (Fed. Cir. 2016).
`
`V. THE BRACCO MANUAL
`Petitioner relies on the Bracco Manual for Ground 3. (Petition at 23.) As the
`
`Board notes in the Decision:
`
`“[W]hether Petitioner has sufficiently established that the Bracco
`Manual was available as prior art can be analyzed further after full
`development of the record. See also 37 C.F.R. § 42.64 (providing
`requirements for objections to evidence, supplemental evidence, and
`motion to exclude). We note that the cover of the Bracco Manual
`indicates that Patent Owner created the Bracco Manual and thus, may
`likely possess information relevant to public accessibility of the Bracco
`Manual in the relevant time frame.” (Decision at 17.)
`
`Patent Owner disagrees that the Bracco Manual qualifies as a printed
`
`publication as of the priority date because the manual was only supplied to customers
`
`and all such customers were under an obligation of confidentiality during the
`
`relevant time period. Cordis Corp. v. Boston Scientific Corp., 561 F.3d 1319, 1333-
`
`1334 (Fed. Cir. 2009). Further, the Challenged Claims are patentable over Klein, so
`
`the confidential status of the Bracco Manual as of the priority date is irrelevant as it
`
`relates to the main basis of unpatentability asserted by Petitioner.
`
`Page 19 of 22
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`
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`IPR2018-01449
`U.S. Patent No. 9,299,467
`VI. DR. MURTHY’S TESTIMONY SHOULD BE ACCORDED LITTLE
`WEIGHT BECAUSE IT IS BASED ON CONJECTURE AND LACKS
`FOUNDATION
`Petitioner used two Declarations in support of its Pe
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