Trials@uspto.gov
`571-272-7822
`
`Paper 30
`Entered: February 6, 2020
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`JUBILANT DRAXIMAGE INC.,
`Petitioner,
`v.
`BRACCO DIAGNOSTICS INC.,
`Patent Owner.
`
`IPR2018-01448
`Patent 9,299,468 B2
`
`
`
`
`
`
`
`
`
`Before HYUN J. JUNG, GEORGE R. HOSKINS, and
`RICHARD H. MARSCHALL, Administrative Patent Judges.
`JUNG, Administrative Patent Judge.
`
`
`
`JUDGMENT
`Final Written Decision
`Determining All Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
`INTRODUCTION
`I.
`We have jurisdiction under 35 U.S.C. § 6. This Final Written
`Decision is issued pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73.
`For the reasons that follow, we determine that Petitioner has shown by a
`
`
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`preponderance of the evidence that claims 1, 2, 4–20, and 24–28 of
`U.S. Patent No. 9,299,468 B2 are unpatentable.
`A. Background and Summary
`Jubilant DraxImage Inc. (“Petitioner”) filed a Petition (Paper 1,
`“Pet.”) requesting institution of an inter partes review of claims 1, 2, 4–20,
`and 24–28 of U.S. Patent No. 9,299,468 B2 (Ex. 1001, “the ’468 patent”).
`Bracco Diagnostics Inc. (“Patent Owner”) filed a Preliminary Response.
`Paper 6. Pursuant to 35 U.S.C. § 314, we instituted an inter partes review of
`the ’468 patent. Paper 7 (“Dec. to Inst.”). In particular, we instituted review
`of claims 1, 2, 4–20, and 24–28 on all presented challenges. Dec. to Inst. 2,
`16, 22.
`After institution, Patent Owner filed a Response (Paper 13, “PO
`Resp.”), to which Petitioner filed a Reply (Paper 14, “Pet. Reply”). We
`authorized via email (1) Patent Owner to file a paper identifying arguments
`in Petitioner’s Reply that Patent Owner believed exceeded proper scope and
`(2) Petitioner to file a paper to identify where the contention Petitioner was
`responding to can be found. Patent Owner filed its authorized paper (Paper
`15), and Petitioner filed its authorized response (Paper 16). Patent Owner
`thereafter filed a Sur-Reply (Paper 17, “PO Sur-Reply”).
`An oral hearing in this proceeding was held on October 29, 2019; a
`transcript of the hearing is included in the record (Paper 26, “Tr.”).
`B. Real Parties in Interest
`Petitioner states that the “real parties-in-interest for this Petition are
`Jubilant DraxImage Inc., Jubilant Pharma Limited, and Jubilant Life Science
`Limited.” Pet. 2. Patent Owner states that “Bracco Diagnostics Inc.
`(‘Bracco’) is the real party-in-interest.” Paper 4, 2.
`
`2
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`C. Related Matters
`The parties indicate that the ’468 patent has been asserted in Bracco
`Diagnostics Inc. v. Jubilant DraxImage Inc., Case No. 3:18-cv-04422
`(D.N.J.). Pet. 2; Paper 4, 2; PO Resp. 5; Ex. 1002 (complaint for patent
`infringement involving the ’468 patent and others). The parties also indicate
`that the district court litigation is stayed pending resolution of Investigation
`No. 337-TA-1110 by the U.S. International Trade Commission (“ITC” or
`“Commission”). Pet. 2 (citing Exs. 1002–1004); PO Resp. 5 (citing
`Exs. 1002–1004); Ex. 1004 (order from civil action no. 3:18-cv-4422
`granting joint motion to stay pending resolution of ITC Investigation No.
`337-TA-1110).
`In the ITC investigation filed March 27, 2018, Bracco Diagnostics,
`Inc. contends that Jubilant DraxImage Inc., Jubilant Pharma Limited, and
`Jubilant Life Sciences violate Section 337 of the Tariff Act of 1930 by
`importing strontium-rubidium infusion systems and components that
`infringe one of U.S. Patent Nos. 9,814,826; 9,750,869; and 9,750,870.
`Ex. 1003, 1, 14. The ’468 patent is not part of the ITC investigation, but
`Patent Owner indicates that the investigation “involv[es] related patents.”
`PO Resp. 5 (citing Exs. 1002–1004). Patent Owner also states that “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.” Id.
`Patent Owner subsequently filed a “Notice of Commission
`Determination to Review in Part a Final Initial Determination Finding No
`Section 337 Violation.” Paper 21; Ex. 2018 (notice from Investigation No.
`337-TA-1110 issued Sept. 30, 2019). The notice states that a Final Initial
`Determination (“FID”) was issued on August 1, 2019, “the FID finds . . . all
`
`3
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`asserted claims are infringed but invalid as obvious over the prior art,” and
`the “Commission has determined to review the FID in part.” Ex. 2018, 2.
`Petitioner filed a “Notice of Commission Final Determination of No
`Violation of Section 337; Termination of the Investigation.” Paper 27, 1;
`Ex. 1047. According to Petitioner, “Ex. 1047 indicates that the Commission
`determined to affirm with modification and to supplement the prior Final
`Initial Determination’s findings with respect to the invalidity of the patent
`claims asserted in the 1110 Investigation.” Paper 27, 1 (citing Ex. 1047, 2);
`Ex. 1047, 2 (stating that “the Commission has determined to affirm with
`modification and to supplement the FID’s findings with respect to the
`invalidity of the asserted patent claims”).
`Petitioner also filed a public version of a Commission Opinion for
`Investigation No. 337-TA-1110. Paper 28; Ex. 1048. Petitioner states that
`the “Commission Opinion addresses several issues that are relevant to the
`present inter partes review.” Paper 28, 1. According to Petitioner, “the
`Commission considered teachings of the Klein and Tate references against
`claim elements that require an eluate reservoir, a shielded well, and a dose
`calibrator to be located ‘on-board a cart’” and held that “Klein, alone or in
`combination with Tate, teaches or discloses such subject matter.” Id. (citing
`Ex. 1048, 13–19). Petitioner also states that “the Commission considered
`teachings of the Klein reference against claim elements that require a
`computer not to allow a patient infusion when a strontium breakthrough test
`result is greater than or equal to an allowed limit” and held that “Klein
`teaches or discloses such subject matter.” Id. (citing Ex. 1048, 24–26).
`Patent Owner has filed an appeal of the Commission Opinion. Ex. 2019.
`
`4
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`The ’468 patent is also challenged in IPR2018-01450, and a related
`patent that claims priority to common applications is challenged in IPR2018-
`01449. Pet. 2; Paper 4, 2; PO Resp. 5.
`D. The ’468 Patent
`The ’468 patent issued March 29, 2016, from an application filed
`August 8, 2014, which is a continuation of an application filed June 11,
`2009, which, in turn, is a continuation of four applications filed June 11,
`2008. Ex. 1001, codes (22), (45), (63), 1:8–21; see also Pet. 9 (asserting that
`the “priority date for the ’468 Patent is June 11, 2009” because the
`applications filed on June 11, 2008 fail to “provide written description
`support for ‘a dose calibrator carried by [a] movable cart’ as required by
`claims 1 and 24”).
`The ’468 patent relates to “systems that generate and infuse
`radiopharmaceuticals.” Ex. 1001, 1:25–26. Figure 1D of the ’468 patent is
`reproduced below.
`
`
`
`5
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`Figure 1D is “a schematic of an infusion circuit.” Id. at 2:10–11.
`Infusion system 10 can be mobile and may incorporate infusion circuit 300,
`a part of which is contained within shielding assembly 200. Id. at 3:52–54,
`4:53–61, Fig. 1A. Infusion circuit 300 includes eluant reservoir 15 that
`contains saline as the eluant, syringe pump 33 that pumps eluant from
`reservoir 15, radioisotope generator 21 through which eluant is pumped to
`create a radioactive eluant, and activity detector 25 that measures the activity
`of the eluant from generator 21. Id. at 4:65–67, 5:2–3, 5:6–7, 5:10–11.
`Activity detector 25 also provides feedback for directing the eluant via
`divergence valve 35WP to either waste bottle 23 or patient line 305p. Id. at
`5:10–14. Divergence valve 35BG directs eluant either to tubing line 304 to
`generator 21 or to by-pass tubing line 303 and patient line 305p. Id. at
`5:41–45.
`“[A]ccording to alternate embodiments, system 10 includes an ‘on
`board’ dose calibrator for quality control tests, and circuit 300 is expanded to
`include elements for an automated collection of eluate samples for activity
`measurements, via the on board dose calibrator,” such as “downstream of
`divergence valve 35WP and in communication with tubing line 305P.” Id.
`at 8:4–12; see also id. at 18:56–60 (stating “some alternate embodiments . . .
`include an on board dose calibrator so that the entire sequence of sample
`collection and calculation steps . . . for the quality control procedures, may
`be automated”).
`Also, in some embodiments, “computer 17 is coupled to a controller
`of system 10” and “monitor 172 of computer 17 not only displays
`indications of system operation for a user of system 10, but also serves as a
`device for user input (e.g. touch screen input).” Id. at 3:28–33. “According
`to some embodiments, system 10 will not allow an infusion if the results
`
`6
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`exceed the acceptable limits, and may present a screen explaining that the
`results are outside the acceptable limits.” Id. at 17:64–67.
`E. Illustrative Claim
`The ’468 patent has 29 claims, of which Petitioner challenges claims
`1, 2, 4–20, and 24–28. Of those, claims 1 and 24 are independent. Claim 1
`is reproduced below.
`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.
`
`7
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`Ex. 1001, 23:60–24:21.
`F. Prior Art and Asserted Grounds
`Petitioner identifies the following references as prior art in the
`asserted grounds of unpatentability:
`U.S. Patent Application Publication No. US 2004/0260143 A1,
`published December 23, 2004 (Ex. 1024, “Reilly”);
`U.S. Patent Application Publication No. US 2008/0177126 A1,
`published July 24, 2008 (Ex. 1025, “Tate”);
`U.S. Patent Application Publication No. US 2008/0242915 A1,
`published October 2, 2008 (Ex. 1023, “Jackson”);
`U.S. Patent Application Publication No. US 2011/0178359 A1,
`published July 21, 2011 (Ex. 1022, “Hirschman”);
`Ran Klein, Precise 82Rb Infusion System for Cardiac Perfusion
`Measurement Using 3D Positron Emission Tomography (2006) (Ex. 1014,
`“Klein”); and
`Bracco Diagnostics Inc., CardioGen-82 Infusion System User’s
`Guide, (rev. 07, 2004) (Ex. 1021, “Bracco Manual”).
`Patent Owner states that “Klein, Reilly, and Tate all appear to be pre-
`AIA §102 prior art as of June 11, 2008.” PO Resp. 8.
`The Petition is supported by a Declaration of Robert T. Stone, Ph.D.
`Ex. 1015. Petitioner also filed a Declaration of Venkatesh L. Murthy, M.D.,
`Ph.D. Ex. 1017. Patent Owner filed a Declaration of Norbert J. Pelc, Sc.D.
`(Ex. 2003) and deposition transcripts for Dr. Stone and Dr. Murthy
`(Exs. 2010, 2016).
`Petitioner asserts that claims 1, 2, 4–20, and 24–28 would have been
`unpatentable on the following grounds:
`
`8
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`Claim(s) Challenged
`1, 2, 4, 6, 7, 9–17, 19,
`24, 25, 28
`8
`
`18, 20, 27
`
`5, 26
`
`Pet. 25–87.
`
`
`
`35 U.S.C. §
`103(a)1
`
`Reference(s)/Basis
`Klein, Reilly, Tate
`
`103(a)
`
`103(a)
`
`103(a)
`
`Klein, Reilly, Tate, the Bracco
`Manual
`
`Klein, Reilly, Tate, Hirschman
`
`Klein, Reilly, Tate, Hirschman,
`Jackson
`
`II. ANALYSIS
`
`A. Legal Standards
`To prevail in its challenges, Petitioner must prove unpatentability by a
`preponderance of the evidence. 35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d).
`A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
`between the subject matter sought to be patented and the prior art are such
`that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which said
`subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
`(2007). The question of obviousness is resolved on the basis of underlying
`factual determinations including: (1) the scope and content of the prior art;
`
`1 The relevant sections of the Leahy-Smith America Invents Act (“AIA”),
`Pub. L. No. 112–29, 125 Stat. 284 (Sept. 16, 2011), took effect on March 16,
`2013. The application from which the ’468 patent issued was filed in
`August 2014, but asserts continuation priority to several applications filed
`before March 2013. Because there is no argument in the record to suggest
`the AIA version of Title 35 applies to the ’468 patent, our citations to Title
`35 are to the pre-AIA version.
`
`9
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`(2) any differences between the claimed subject matter and the prior art;
`(3) the level of ordinary skill in the art; and (4) objective evidence of
`nonobviousness. See Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`As discussed below, the parties’ disputes are related to the level of
`ordinary skill in the art, the scope and content of the prior art, and the
`differences between the prior art and claims 1, 2, and 24. The parties do not
`present any objective evidence of nonobviousness.
`After reviewing the complete record, we conclude that Petitioner has
`shown by a preponderance of the evidence that the asserted references teach
`or suggest each limitation of claims 1, 2, 4–20, and 24–28; that a person of
`ordinary skill in the art would have had a reason to modify or combine the
`asserted references; and that a person of ordinary skill in the art would have
`had a reasonable expectation of success in modifying or combining the
`asserted references.
`B. Level of Ordinary Skill in the Art
`Petitioner contends that a person having ordinary skill in the art would
`have a
`graduate’s degree with some emphasis in equipment design,
`automation, or controls, such as electrical engineering, systems
`engineering, mechanical engineering, or a related field, or an
`undergraduate degree in such fields with two to three years’ work
`experience in radioactive protection systems or in medical device
`product,
`automation,
`or
`instrumentation
`design
`and
`development, including work with prototypes and finished
`commercial products.
`Pet. 10 (citing Ex. 1015 ¶¶ 32–42). Petitioner also contends that “[s]uch a
`person would have had a basic understanding, through education or
`experience, of general design control principles and processes and practices
`for partial or full automation of existing processes or test procedures.” Id.
`
`10
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`(citing Ex. 1015 ¶¶ 32–42). Petitioner further argues that Patent Owner’s
`proposed level of ordinary skill in the related ITC case is flawed because the
`claims challenged in this proceeding additionally recite a computer that
`automates procedures previously manually performed by medical personnel
`and “[m]edical personnel like those suggested by the Patent Owner lack the
`education and experience to develop the hardware and software controls for
`such computer-controlled systems or to design radiation shielding.” Id. at
`10–11 (citing Ex. 1015 ¶¶ 32–42; Ex. 1021; Ex. 1039).
`Patent Owner asserts that a person of ordinary skill in the art “would
`generally have a graduate degree in medicine and/or in a medical related
`science, including physics, chemistry, biology, physiology, and/or
`biophysics, and would generally have at least some clinical, research and/or
`design experience with respect to PET imaging and/or PET imaging
`systems.” PO Resp. 6–7 (citing Ex. 2003 ¶ 27). Patent Owner also asserts
`that “[a]n individual with an undergraduate degree along with significant
`experience could also be sufficiently skilled,” “the amount of experience
`following an undergraduate degree would depend on the level of formal
`education and amount of experience working with radiopharmaceuticals,”
`and “such a person may be working as part of a team.” Id. at 7–8 (citing
`Ex. 2003 ¶¶ 27–29).
`Patent Owner argues that Petitioner’s proposed level of ordinary skill
`is improper because it “does not actually require familiarity with elution of
`radioactive isotopes, PET imaging, or even systems employing any form of
`radioactive substance.” Id. at 7. Patent Owner also argues that Petitioner is
`“attempt[ing] to open the door to considering any instrumentation design or
`medical device design background, while ignoring that one of ordinary skill
`in the art would be particularly hesitant to make any changes to a system
`
`11
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`involving radioactive materials when that system has serious design
`concerns specifically associated with radioactivity.” Id. Patent Owner
`further states that “the parties disagree regarding the [person of ordinary skill
`in the art] definition, both here and in the ITC.” Id. at 6 (citing Pet. 10–11).
`Patent Owner contends that “Petitioner has failed to show that the
`Challenged Claims are invalid under either party’s proposed level of skill.”
`Id. at 8. Petitioner replies that “[a]lthough the parties define [person of
`ordinary skill in the art] differently, neither party argues that the differences
`between them are material to the outcome of this IPR.” Pet. Reply 1–2.
`In determining the level of ordinary skill in the art, various factors
`may be considered, including the “type of problems encountered in the art;
`prior art solutions to those problems; rapidity with which innovations are
`made; sophistication of the technology; and educational level of active
`workers in the field.” In re GPAC Inc., 57 F.3d 1573, 1579 (Fed. Cir. 1995)
`(citation and internal quotation marks omitted).
`Klein addresses the development of a system for eluting a constant
`rate of activity. See Ex. 1014, 1 (“The goal of this project is to develop a
`system that is capable of eluting 82Rb at a constant rate of activity from a
`82Sr/82Rb generator for use in a clinical and experimental setting.”). Reilly
`similarly states a “desir[e] to develop devices, systems and methods through
`which toxic or hazardous pharmaceuticals (for example,
`radiopharmaceuticals) can be administered in controlled manner to enhance
`their effectiveness and patient safety, while reducing exposure of
`administering personnel to such hazardous pharmaceuticals.” Ex. 1024 ¶ 16.
`Tate likewise states that “[i]t has long been recognized as very
`desirable to develop devices, systems, components and methods for
`calculating and delivering accurate and effective doses of
`
`12
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`radiopharmaceuticals to patients, while reducing the exposure of
`administering or other medical personnel to such hazardous
`pharmaceuticals.” Ex. 1025 ¶ 11. Jackson similarly describes “a need to
`improve the quality control of the administration of radiopharmaceuticals to
`patients” and “a need to reduce the exposure of people, such as PET
`technicians, to radioactivity during the manual steps of administering a
`radiopharmaceutical to patients.” Ex. 1023 ¶ 11. According to Hirschman,
`“a need exists for integrated systems and methods capable of the generation,
`preparation, and administration of pharmaceutical substances . . . such as
`radioactive pharmaceutical substances.” Ex. 1022 ¶ 18.
`Based on the full record before us, because the asserted references
`describe the problems and solutions of accurately delivering
`radiopharmaceuticals, reducing radiation exposure to operators, and
`integrating systems related to radiopharmaceuticals, we find that Petitioner’s
`proposed level of ordinary skill in the art, which includes understanding of
`equipment control, “radioactive protection systems,” and equipment design,
`is more consistent with the prior art of record than Patent Owner’s proposal.
`Pet. 10 (citing Ex. 1015 ¶¶ 32–42). We, therefore, apply Petitioner’s
`proposed level of skill to our analysis.
`We also determine that the parties’ competing proposals regarding the
`level of ordinary skill agree in certain aspects. For example, both parties
`propose at least a graduate degree, albeit in different concentrations of study.
`See Pet. 10 (“graduate’s degree with some emphasis in equipment design,
`automation, or controls, . . . or a related field”); PO Resp. 6–7 (“a graduate
`degree in medicine and/or in a medical related science”). Both parties also
`alternatively propose that the ordinarily skilled artisan would have had “an
`undergraduate degree in such fields with two to three years’ work experience
`
`13
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`in radioactive protection systems or in medical device product, automation,
`or instrumentation design and development, including work with prototypes
`and finished commercial products” (Pet. 10) or “an undergraduate degree
`along with significant experience,” “the amount of experience following an
`undergraduate degree would depend on the level of formal education and
`amount of experience working with radiopharmaceuticals” (PO Resp. 7–8).
`We further determine that Petitioner’s proposed ordinarily skilled
`artisan with “an undergraduate degree in [equipment design, automation, or
`controls, or a related field] with two to three years’ work experience . . . in
`medical device product, automation, or instrumentation design and
`development” (see Pet. 10) would overlap, at least in part, Patent Owner’s
`proposal of a person having “a graduate degree in medicine and/or in a
`medical related science” and “at least some . . . design experience with
`respect to . . . PET imaging systems” (see PO Resp. 6–7). We, thus,
`determine that any differences between the parties’ proposed level of skill
`would not affect our analysis below. See also Pet. Reply 1–2 (“Although the
`parties define [person of ordinary skill in the art] differently, neither party
`argues that the differences between them are material to the outcome of this
`IPR.”).
`C. Claim Construction
`In the present inter partes review, claim terms in the ’468 patent,
`which is unexpired, are interpreted according to their broadest reasonable
`construction in light of the Specification of the ’468 patent. 37 C.F.R.
`§ 42.100(b) (2017); Cuozzo Speed Techs. LLC v. Lee, 136 S. Ct. 2131,
`
`14
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`2144–46 (2016) (upholding the use of the broadest reasonable interpretation
`standard).2
`Petitioner states that “[a]ll claim terms have been assigned their
`ordinary and customary meaning in this analysis.” Pet. 12. “Patent Owner
`believes that no specific constructions are required at this time” (PO
`Resp. 6), and Petitioner replies that “[t]here are no claim construction issues
`in dispute” (Pet. Reply 1). See also Tr. 8:14–19 (Petitioner’s counsel
`agreeing that no claim term in this proceeding needs express interpretation).
`We agree with the parties that no express interpretation is required for
`any claim term. Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795,
`803 (Fed. Cir. 1999) (construing explicitly only those claim terms in
`controversy and only to the extent necessary to resolve the controversy); see
`also Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co., 868 F.3d
`1013, 1017 (Fed. Cir. 2017) (applying Vivid Techs. in the context of an inter
`partes review).
`D. Scope and Content of the Prior Art
`Petitioner contends that June 2008 is “the earliest date to which the
`’468 Patent claims priority” but that the “proper priority date for the ’468
`
`2 On October 11, 2018, the Office revised its rules to harmonize the Board’s
`claim construction standard with that used in civil actions under 35 U.S.C.
`§ 282(b) in federal district court. Changes to the Claim Construction
`Standard for Interpreting Claims in Trial Proceedings Before the Patent Trial
`and Appeal Board, 83 Fed. Reg. 51,340 (Oct. 11, 2018) (amending 37
`C.F.R. § 42.100(b) effective November 13, 2018). This rule change does
`not apply here. See Paper 3, 1 (according filing date of August 22, 2018 to
`the Petition); PO Resp. 6 (stating that the “present IPR was filed before the
`new IPR rules regarding claim construction were implemented”); see also
`Pet. 12 n.1 (arguing that “[i]f the Patent Office were to adopt the same claim
`construction standard as used in district court proceedings, the analysis
`would remain the same”).
`
`15
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`Patent is June 11, 2009” because the written description support for “a dose
`calibrator carried by [a] movable cart” first appeared in an application filed
`on June 11, 2009. Pet. 1, 9 (citing Ex. 1010, 1196).
`Patent Owner disagrees but states that “it is immaterial to this IPR
`whether June 11, 2008 or June 11, 2009 is the correct priority date as the
`cited art of Klein, Reilly, and Tate all appear to be pre-AIA §102 prior art as
`of June 11, 2008.” PO Resp. 8 (citing Pet. 9). Thus, because there is no
`priority dispute that would determine whether any of the references involved
`here are early enough to be prior art, there is nothing for us to decide in this
`regard.
`Patent Owner also disputes that the Bracco Manual is a printed
`publication (id. at 58), which we address below in connection with the
`parties’ arguments regarding claim 8, against which Petitioner asserts the
`Bracco Manual along with other references.
`1. Klein (Ex. 1014)
`Klein is a student thesis that “describes the development of a
`Rubidium-82 (82Rb) infusion system for use in positron emission
`tomography (PET)” and “is based on a 82Sr/82Rb generator which produces
`82Rb activity continuously.” Ex. 1014, 13; see also id. at 8 (“82Rb can be
`supplied using a 82Sr/82Rb generator.”)
`“The goal of this project is to develop a system that is capable of
`eluting 82Rb at a constant rate of activity from a 82Sr/82Rb generator for use
`in a clinical and experimental setting.” Id. at 1. Klein “introduces the
`
`
`3 Our citations to Klein are to the page numbers found in the bottom center
`of each page.
`
`16
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`second generation 82Rb elution system (RbES).” Id. Figures 2-2, 2-3, and
`2-4 of Klein are reproduced below. Id. at 19.
`
`
`
`
`
`17
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`
`
`
`Figure 2-2 is a hardware component diagram of an RbES prototype.
`Ex. 1014, 19. Figure 2-3 is a “[p]hotograph of the assembled 82Rb elution
`system and its components,” and Figure 2-4 is a “[p]hotograph of top cover
`of the 82Rb elution system.” Id. at 24.
`Klein includes a personal computer that interfaces with sensors and
`actuators to allow flow of saline through a 82Sr/82Rb generator or a bypass
`line to the patient, dose calibrator, or waste container. Id. at 19. Klein states
`that “using a PC to control the system” allows for a “wide range of
`applications and devices that are readily supported” including “off-the-shelf
`user interface devices, as well as machine interfaces and data acquisition
`devices” Id. at 20.
`“All the components are assembled in a stainless steel cart.” Id. at 23.
`The “generator was placed in the cart and surrounded by lead rings to
`provide maximum radiation shielding” from which “82Rb is eluted in the
`form of 82RbCl (eluate).” Id. at 8, 23; see also id. at 34 (stating that the
`
`18
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`“waste container is located on the top shelf inside the cart and is contained
`within lead shielding to minimize exposure to the operator”).
`“All the saline lines were mounted on a modified top cover” (id. at
`23), and “[a]lthough the generator and waste container are shielded by lead,
`the saline lines are a source of radiation during elutions” (id. at 36).
`Klein also includes flow control valves, an activity counter, pumps,
`and a pressure sensor. Id. at 21–23. Klein states that “real-time software
`controls the pumps and valves” to “affect the flow of saline through the
`generator or its bypass line to the patient, dose calibrator, or waste
`container.” Id. at 19. The system acquires data from the activity counter
`and dose calibrator. Id. The “activity counter was included in the design to
`allow data collection and monitoring of the elution of activity” so as to
`“develop[] a controller capable of directing saline through the generator or
`its bypass line by actuating the generator valve in order to achieve a constant
`rate of activity using feedback from the activity counter.” Id. at 71.
`According to Klein, the “system is required to operate in a clinical
`setting and therefore must be reliable, easy to operate, and above all, safe.”
`Id. at 26. Klein also states that “82Sr and 85Sr ‘breakthrough’ can result if the
`generator is used indefinitely” and “[i]n high quantities these compounds
`may have ill effects on health.” Id. at 9. Klein describes that if there is an
`indication of excessive strontium breakthrough, then “elution to patients
`should be avoided.” Id. at 10; see also id. at 33 (stating that the “amount of
`Sr breakthrough activity must be strictly limited to the Health Canada
`guidelines”).
`The dose calibrator “is utilized in the system for both calibration and
`testing” and “is used to detect the breakthrough activity as part of the
`calibration test through measurement of 82Rb activity.” Id. at 19, 23, 50.
`
`19
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`Klein’s system is calibrated “by monitoring an external dose calibrator
`during the calibration run” (id. at 17) and “[w]ait[s] for decay to read
`breakthrough from dose calibrator” (id. at 64). The “dose calibrator is used
`to detect the breakthrough activity . . . through measurement of 82Rb
`activity” and the “breakthrough of each isotope, A82Sr/A82Rb and A85Sr/A82Rb,
`is calculated as a relative activity ratio of Sr activity to 82Rb activity
`delivered.” Id. at 50–51.
`Klein also describes a daily protocol “intended for routine system
`maintenance, system diagnostics, and clinical preparation of the system,”
`which includes a calibration run. Id. at 17–18. Klein states that “[o]nly after
`a calibration run with low Sr breakthrough has been successfully completed
`can patient elutions be carried out,” and “[o]nce the daily protocol has been
`completed successfully, patient elutions are enabled until the end of the
`day.” Id. at 18; see also id. at 33 (stating that the “issue is addressed by
`daily breakthrough tests as part of the daily protocol ensured by the
`system”), 43 (stating that “certain maintenance measures must be carried out
`as dictated by the daily protocol” and “Sr breakthrough must be measured
`and a complete system test must follow”), 50–52 (describing breakthrough
`measurement), 122 (stating “[d]aily 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”). Klein also states that 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.
`
`20
`
`

`

`IPR2018-01448
`Patent 9,299,468 B2
`2. Reilly (Ex. 1024)
`Reilly relates to “deliver