`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`JUBLIANT DRAXIMAGE INC.,
`Petitioner,
`
`v.
`
`BRACCO DIAGNOSTICS INC.,
`Patent Owner.
`
`Case IPR2018-01449
`Patent 9,299,467
`
`PETITIONER'S DEMONSTRATIVE EXHIBITS
`
`Mail Stop: PATENT BOARD
`Patent Trial and Appeal Board
`U.S. Patent & Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`IPR 2018‐01449
`IPR 2018‐01448 | IPR 2018‐01450
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`1
`
`
`
`Claim 1
`
`1. A system comprising:
`a shielding assembly configured to contain a radioisotope
`generator that generates radioactive eluate via elution;
`a computer carried by the shielding assembly, wherein the
`computer is configured to receive a user input and,
`responsive to receiving the user input, control the
`radioisotope generator to generate a sample of eluate via
`elution during breakthrough testing; and
`a dose calibrator electronically coupled to the computer
`and configured to measure an activity of the sample of
`eluate generated during breakthrough testing,
`wherein the computer carried by the shielding assembly is
`configured to receive the activity data from the dose
`calibrator and calculate breakthrough test results, and
`the computer is further configured to prevent a patient
`infusion procedure if a breakthrough test result exceeds an
`allowable limit.
`
`Claim 13
`13. A method comprising:
`generating, with a radioisotope generator contained within
`a shielding assembly, a radioactive eluate via elution of an
`eluant;
`measuring, with a dose calibrator electronically coupled to
`a computer carried by the shielding assembly, an activity of
`the radioactive eluate;
`determining, with the computer, an activity of rubidium‐82
`within the radioactive eluate, and
`preventing, with the computer, a patient infusion
`procedure if a breakthrough test result exceeds an
`allowable limit.
`
`October 29, 2019
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`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`2
`
`
`
`Claim 1
`1. A mobile radioisotope generator system comprising:
`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 configured to generate a
`radioactive eluate via elution of an eluant,
`the infusion tubing circuit including a tubing line connected between the
`strontium/rubidium radioisotope generator and the dose calibrator and
`configured to supply a portion of radioactive eluate to the dose calibrator,
`the activity detector being positioned downstream of the
`strontium/rubidium radioisotope generator and configured to measure an
`activity of the radioactive eluate flowing through the infusion tubing circuit,
`and
`the computer being electronically coupled to the dose calibrator and
`configured to execute automated quality control testing using the dose
`calibrator,
`wherein the computer is configured to determine an activity of strontium‐82
`and an activity of strontium‐85 in the portion of radioactive eluate through
`automated quality control testing using the dose calibrator,
`the computer is configured to control the mobile radioisotope generator
`system to deliver a dose of radioactive eluate to a patient during a patient
`infusion procedure, and
`the computer is further configured to prevent the patient infusion
`procedure if a quality control test result exceeds an allowable limit.
`
`Claim 24
`
`24. A method comprising:
`delivering eluant to a strontium/rubidium radioisotope generator carried by
`a movable cart and thereby generating radioactive eluate via elution;
`measuring, with an activity detector carried by the movable cart, an activity
`of the eluate within a tubing line of an infusing tubing circuit;
`delivering a portion of eluate via the tubing line to a dose calibrator carried
`by the movable cart,
`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.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`3
`
`
`
`Claim 21
`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;
`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‐82
`or the activity of strontium‐85 exceeds an allowable limit.
`
`October 29, 2019
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`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`4
`
`
`
`Claim 1
`1. A system comprising:
`a shielding assembly configured to contain a
`radioisotope generator that generates radioactive
`eluate via elution;
`a computer carried by the shielding assembly,
`wherein the computer is configured to receive a
`user input and, responsive to receiving the user
`input, control the radioisotope generator to
`generate a sample of eluate via elution during
`breakthrough testing; and
`a dose calibrator electronically coupled to the
`computer and configured to measure an activity of
`the sample of eluate generated during
`breakthrough testing,
`wherein the computer carried by the shielding
`assembly is configured to receive the activity data
`from the dose calibrator and calculate
`breakthrough test results, and
`the computer is further configured to prevent a
`patient infusion procedure if a breakthrough test
`result exceeds an allowable limit.
`
`October 29, 2019
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`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`5
`
`
`
`Claim 1
`1. A system comprising:
`a shielding assembly configured to contain a
`radioisotope generator that generates radioactive
`eluate via elution;
`a computer carried by the shielding assembly,
`wherein the computer is configured to receive a
`user input and, responsive to receiving the user
`input, control the radioisotope generator to
`generate a sample of eluate via elution during
`breakthrough testing; and
`a dose calibrator electronically coupled to the
`computer and configured to measure an activity of
`the sample of eluate generated during
`breakthrough testing,
`wherein the computer carried by the shielding
`assembly is configured to receive the activity data
`from the dose calibrator and calculate
`breakthrough test results, and
`the computer is further configured to prevent a
`patient infusion procedure if a breakthrough test
`result exceeds an allowable limit.
`
`October 29, 2019
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`
`6
`
`
`
`‘467 Patent
` IPR2018‐01449:
` Ground 1:
`Whether Klein discloses a computer “configured to prevent a patient infusion procedure
`if a breakthrough test result exceeds an allowable limit.”
` Ground 3:
`Whether the CardioGen product manual qualifies as a printed publication.
` Murthy Dec.:
`Effect of Dr. Murthy’s declaration.
`Pet. Reply (‐1449) at 2.
` IPR2018‐01448:
`‘468 Patent, claims 1‐2, 4‐19 & 24‐28
` Ground 1:
`• Whether Klein discloses a computer lockout,
`• Whether would have been obvious to move Klein’s dose calibrator from an adjacent counter to a “movable platform.”
` Ground 2:
`Whether the CardioGen product manual qualifies as a printed publication.
` Murthy Dec.:
`Effect of Dr. Murthy’s declaration.
`Pet. Reply (‐1448) at 2.
` IPR2018‐01450:
`‘468 Patent, claims 21‐23
` Whether Klein discloses a means that performs the lockout function.
` Whether the CardioGen product manual qualifies as a printed publication.
`
`Pet. Reply (‐1450) at 3.
`
`October 29, 2019
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`7
`
`
`
`Ground 1
`Ground 1
`Ground 1
`
` Computer “lockout” limitations.
` IPR2018‐01449
`’467 Patent
` IPR2018‐01448
`’468 Patent claims 1‐2, 4‐19, 24‐28
` IPR2018‐01450
`’468 Patent claims 21‐23
` Placing dose calibrator on a movable cart is obvious.
`Ground 1
` IPR2018‐01448
`’468 Patent claims 1‐2, 4‐19, 24‐28
` The Bracco Manual qualifies as a printed publication.
` IPR2018‐01449
`’467 Patent
`Ground 3
` IPR2018‐01448
`’468 Patent claims 1‐2, 4‐19, 24‐28
`Ground 2
` IPR2018‐01450
`’468 Patent claims 21‐23
`N/A
` Dr. Murthy’s declaration.
` IPR2018‐01449
`’467 Patent
` IPR2018‐01448
`’468 Patent claims 1‐2, 4‐19, 24‐28
` IPR2018‐01450
`’468 Patent claims 21‐23
`
`N/A
`N/A
`N/A
`
`October 29, 2019
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`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
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`8
`
`
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`9
`
`
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent a patient infusion procedure if a breakthrough test result
`exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient infusion procedure if a breakthrough test result exceeds an
`allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent the patient infusion procedure if a quality control test result
`exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`10
`
`
`
` Klein: Computer/User Interface
`“The user interface must be informative, allow the operator to control all the
`features of the elution system, but also limit the user input to ensure validity.”
`“The interface must be solely through the touch screen which will display a
`keypad and exit button. Other buttons and radio‐buttons must be added only at
`relevant states and immediately removed at the end of each state.”
`Ex. 1014 at 30‐31; see Pet. (‐1449) at 27‐28; Pet. Reply (‐1449) at 3‐4.
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`11
`
`
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
` Klein: Computer Disables Elutions Daily
`“At the start of each day a flush and calibration run must performed prior
`to patient elution runs. At midnight the calibration and flush expire.”
`Ex. 1014 at 19; see Pet. Reply (‐1449) at 5.
`
`Ex. 1014 at 19.
`“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).”
`
`Ex. 1014 at 44; see Pet. Reply (‐1449) at 6.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`12
`
`
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
` Klein: Computer Ensures Daily Protocol is Followed.
`“Only after a calibration run with low Sr breakthrough has been
`successfully completed can patient elutions be carried out. … Once the
`daily protocol has been completed successfully, patient elutions are
`enabled until the end of the day.”
`
`Ex. 1014 at 18; see Pet. Reply (‐1449) at 6.
`
`Ex. 1014 at 19.
`“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).”
`
`Ex. 1014 at 44; see Pet. Reply (‐1449) at 6.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`13
`
`
`
` Klein: Computer Ensures Daily Protocol is Followed.
`“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.”
`Ex. 1014 at 29; see Pet. Reply (‐1449) at 6.
`“The software ensured that the daily protocol (discussed below) is
`followed and generated a recording of each elution.”
`Ex. 1014 at 17; see Pet. Reply (‐1449) at 6.
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`14
`
`
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
` What does Bracco Say?
`“[N]owhere does Klein ever expressly state that Klein’s computer
`prevents patient infusions if a strontium breakthrough test result
`exceeds an allowable limit.”
`POR (‐1449) at 13.
`“Klein describes an experiment conducted to specifically observe
`excessive breakthrough and to study how it changes over time once it
`occurs.”
`
`POR (‐1449) at 14.
`“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…. [I]t is the operator, not
`Klein’s computer, who decides whether to allow (or prevent) patient
`infusions if a strontium breakthrough test result exceeds an allowable
`limit.”
`
`POR (‐1449) at 16‐18.
`
`October 29, 2019
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`
`15
`
`
`
` What does Bracco Say?
`“[N]owhere does Klein ever expressly state that Klein’s computer
`prevents patient infusions if a strontium breakthrough test result
`exceeds an allowable limit.”
`POR (‐1449) at 13.
` Bracco’s Expert (Dr. Pelc):
`“The Klein thesis discloses that the system is locked out until you do the
`calibration run. It's absolutely clear that Klein intends his system to
`require that that calibration run be done before patient elutions are
`done for the day, and then at midnight, that permission expires, and you
`have to redo the calibration run.”
`Ex. 2012 (‐1449) at 981:9‐14; see Pet. Reply (‐1449) at 5.
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`16
`
`
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
` What does Bracco Say?
`“[N]owhere does Klein ever expressly state that Klein’s computer
`prevents patient infusions if a strontium breakthrough test result
`exceeds an allowable limit.”
`POR (‐1449) at 13.
` Anticipation does not demand word‐for‐word
`correspondence.
`In re Bond.
`Whether “one skilled in the art would reasonably understand or infer
`from the prior art reference’s teaching that every claim [limitation] was
`disclosed in that single reference.”
`CRFD Research v. Matal; see Pet. Reply at 7.
` Klein:
`“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.”
`Ex. 1014 at 29; see Pet. Reply (‐1449) at 6.
`
`October 29, 2019
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`17
`
`
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
` What does Bracco Say?
`“Klein describes an experiment conducted to specifically observe
`excessive breakthrough and to study how it changes over time once
`it occurs.”
`POR (‐1449) at 14‐15.
` Klein’s Experiments Do Not Involve Patient Infusions.
`“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.…
`We continued to use the generator on the development system past the
`specifications and experienced first breakthrough after approximately
`40L were eluted through the generator. Once breakthrough appeared, it
`was tracked over two months.”
`
`Ex. 1014 at 122; see Pet. Reply (‐1449) at 8.
`“Following is a prompt for a user ID code, which is useful for avoiding
`tampering by unauthorized personnel as well as enabling test runs,
`which were commonly used during the development cycle, but have no
`clinical application.”
`
`Ex. 1014 at 53; see Pet. Reply (‐1449) at 9.
`
`October 29, 2019
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`18
`
`
`
` What does Bracco Say?
`Klein, FIG. 3‐15 confirms that operators (not computers) decide whether
`to prevent patient infusions if strontium breakthrough limits are
`exceeded.
`POR (‐1449) at 16‐18.
` Bracco’s Expert (Dr. Pelc):
`“I interpret this to say that a successful
`calibration run in Klein means you went
`through these steps.”
`Ex. 2012 (‐1449) at 982:25‐983:2.
`
` ‘467 Patent, Claim 1:
`the computer is further configured to prevent
`a patient infusion procedure if a breakthrough
`test result exceeds an allowable limit.
` ‘467 Patent, Claim 13:
`preventing, with the computer, a patient
`infusion procedure if a breakthrough test
`result exceeds an allowable limit.
` ‘468 Patent, Claim 1:
`the computer is further configured to prevent
`the patient infusion procedure if a quality
`control test result exceeds an allowable limit.
` ‘468 Patent, Claim 21:
`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.
`
`October 29, 2019
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`19
`
`
`
` Dr. Pelc’s Full Testimony:
`“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.”
`
`Ex. 2012 (‐1449) at 982:25‐983:6.
` Klein Defines “Success” Differently:
`“Only after a calibration run with low Sr breakthrough has been
`successfully completed can patient elutions be carried out.”
`Ex. 1014 at 18; see Pet. Reply (‐1449) at 11.
`
`October 29, 2019
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`20
`
`
`
` Dr. Pelc’s Full Testimony:
`“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.”
`
`Ex. 2012 at 982:25‐983:6.
` Klein’s System Ensure the Daily Protocol is Followed,
`not Operators:
`“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.”
`Ex. 1014 at 29; see Pet. Reply (‐1449) at 6, 11.
`
`October 29, 2019
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`
`21
`
`
`
`October 29, 2019
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`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`22
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to generate a
`radioactive eluate via elution of an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing line to a dose calibrator carried by the movable cart,
`
`October 29, 2019
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`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`23
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
` Klein: Discloses Claimed Components Operating as
`Claimed.
` Tubing circuit (pink)
` Activity detector (purple)
` Dose calibrator (blue)
` Computer (green)
` Strontium/rubidium generator (red)
`
`Pet. (‐1448) at 26, 30‐38.
`
`October 29, 2019
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`
`Pet. (‐1448) at 14, 31.
`
`24
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
` Klein: All Components on Movable Cart Except Dose
`Calibrator.
` Tubing circuit (pink)
` Activity detector (purple)
` Computer (green)
` Strontium/rubidium generator (red)
`
`Pet. (‐1448) at 26, 30‐38.
`
` Dose Calibrator on Nearby Shelf.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`Pet. (‐1448) at 15, 31.
`
`25
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
` Klein’s Off‐Cart Dose Calibrator: Performs the same
`function as the on‐board dose calibrator claimed by
`the ‘468 Patent.
`Pet. (‐1448) at 11.
`“If a technique has been used to improve one device, and a person of
`ordinary skill in the art would recognize that it would improve similar
`devices in the same way, using the technique is obvious unless its actual
`application is beyond his or her skill.”
`KSR at 417; see Pet. Reply (‐1448) at 12; Anderson’s‐Black Rock.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`26
`
`
`
` Tate Teaches to Place a Dose Calibrator on a Mobile
`Cart
`
`Pet. (‐1448) at 35; Pet. Reply (‐1448) at 13.
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`27
`
`
`
` Reilly Teaches to Place a Dose Calibrator on a
`Common Chassis
`
`Pet. (‐1448) at 34; Pet. Reply (‐1448) at 13
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`28
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
` Motivation to Combine
` The infusion systems of Klein, Reilly and Tate include:
`• Radioactive source
`• Saline source
`• Dose calibrator
`• Waste container
`• Patient tubing
`
`Pet (‐1448) at 27.
` All systems computer‐controlled.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`29
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
` Motivation to Combine: All references describe
`application to rubidium‐82.
`Klein:
`“Precise 82RB Infusion System For Cardiac Perfusion Measurement Using
`3D Positron Emission Tomography”
`
`Ex. 1014 at 1 ; see Pet. (‐1448) at 27.
`
`Tate:
`“To minimize the radiation dose to patients, radiopharmaceuticals
`containing radioisotopes, such as Flourine‐18, Technetium‐99, Carbon‐
`11, Copper‐64, Gallium‐67, Iodine‐123, Nitrogen‐13, Oxygen‐15,
`Rubidium‐82, Thallium‐201, Chromium‐51, Iodine‐131, Iodine‐151,
`Iridium‐192, Phosphorus‐32, Samarium‐153, and Yttrium‐90, having
`relatively short half‐lives are typically used for PET and SPECT imaging
`procedures and other radio‐therapies.”
`
`Ex. 1025 ¶ 7; see Pet. (‐1448) at 27.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`30
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
` Motivation to Combine
` A skilled worker would recognize Klein’s system as a university
`prototype.
` Skilled worker would look to Tate and Reilly for design options when
`preparing Klein’s design for marketplace.
`
`Pet. (‐1448) at 28.
`
`October 29, 2019
`
`DEMONSTRATIVE EXHIBIT – NOT EVIDENCE
`
`31
`
`
`
` ‘468 Patent, Claim 1:
`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 configured to
`generate a radioactive eluate via elution of
`an eluant,
` ‘468 Patent, Claim 24:
`delivering a portion of eluate via the tubing
`line to a dose calibrator carried by the
`movable cart,
`
` What Does Bracco Say? Motivation is lacking because
`“There are significant differences between a strontium‐rubidium elution‐
`infusion system and an FDG infusion system.”
`POR (‐1448) at 11.
`“Klein’s dose calibrator is required to make highly sensitive and critical
`measurements and it cannot be moved or vibrated.”
`
`POR (‐1448) at 26.
`“Moving the dose calibrator onto Klein’s cart would also potentially
`expose the dose calibrator to additional high and/or variable sources of
`radiation.”
`POR (‐1448) at 29.
`“Moving Klein’s dose calibrator onto Klein’s cart would require a system
`redesign.”
`POR (‐1448) at 33.
`“Reilly’s and Tate’s dose calibr