UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`Jubilant DraxImage Inc.,
`
`Petitioner
`
`v.
`
`Bracco Diagnostics Inc.
`
`Patent Owner
`
`
`
`
`
`
`
`
`U.S. Patent No. 9,299,467
`
`
`Inter Partes Review Case No.: IPR2018-01449
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,299,467
`
`
`
`Mail Stop: PATENT BOARD
`Patent Trial and Appeal Board
`U.S. Patent & Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`

`

`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`
`TABLE OF CONTENTS
`
`III.
`
`Page
`Table of Authorities ................................................................................................. iii
`Exhibit List ................................................................................................................ iv
`I.
`Introduction ...................................................................................................... 1
`II. Mandatory Notices Pursuant to 37 C.F.R. § 42.8 ............................................ 2
`A.
`Real Parties-in-Interest (37 C.F.R. § 42.8(b)(1)) .................................. 2
`B.
`Related Matters (37 C.F.R. § 42.8(b)(2)) .............................................. 2
`C.
`Lead and Backup Counsel and Service Information (37 C.F.R.
`§§ 42.8(b)(3)-(4)) .................................................................................. 2
`37 C.F.R. §§ 42.103, 42.104 Requirements .................................................... 3
`A.
`Payment of Fees .................................................................................... 3
`B.
`Grounds for Standing (37 C.F.R. § 42.104(a)) ..................................... 3
`IV. The ’467 Patent ................................................................................................ 4
`A.
`Summary of the ’467 Patent .................................................................. 4
`B.
`Prosecution History ............................................................................... 6
`1.
`The Prior Applications ................................................................ 6
`2.
`The ’623 Application .................................................................. 8
`3.
`New Question of Patentability .................................................... 9
`Level of Skill in the Art ................................................................................. 10
`V.
`VI. Claim Constructions ...................................................................................... 12
`VII. Summary of the Prior Art .............................................................................. 12
`A. Klein (Ex. 1014) .................................................................................. 14
`B.
`Tate (Ex. 1022) .................................................................................... 18
`C.
`Bracco Manual (Ex. 1021) .................................................................. 19
`VIII. The Challenged Claims Are Unpatentable .................................................... 22
`Ground 1: Klein Anticipates Claims 1-4, 6-7, 9-10, 12-16, and 18-20. .... 23
`Ground 2: Klein and Tate Render Claims 11 and 22 Obvious. ................. 56
`A. Motivation to Combine Reference Teachings .......................... 57
`B.
`No Secondary Considerations ................................................... 60
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`Analysis of Challenged Claims ................................................. 60
`C.
`Ground 3: Claims 8 and 21 Are Obvious Over Klein and the Bracco
`Manual. ................................................................................................ 64
`A. Motivation to Combine References .......................................... 65
`B.
`No Secondary Considerations ................................................... 67
`C.
`Analysis of the Challenged Claims ........................................... 67
`IX. Conclusion ..................................................................................................... 68
`
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`
`ii
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Jazz Pharma. Inc. v. Amneal Pharma. LLC,
`2018 WL 3400764 (Fed. Cir. 2018) ................................................................... 17
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) .................................................................... 60, 67
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ................................................................................ 59, 60, 65
`In re Translogic Tech., Inc.,
`504 F.3d 1249 (Fed. Cir. 2007) .......................................................................... 12
`Statutes
`35 U.S.C. §§ 102(a), (b), (e) .............................................................................. 17, 23
`35 U.S.C. § 314(a) ................................................................................................... 22
`Other Authorities
`10 C.F.R. § 20 .......................................................................................................... 58
`21 C.F.R. § 820 ........................................................................................................ 58
`37 C.F.R. § 42.15(a) ................................................................................................... 3
`37 C.F.R. § 42.8 ......................................................................................................... 2
`37 C.F.R. § 42.100(b) .............................................................................................. 12
`37 C.F.R. §§ 42.103, 42.104 ...................................................................................... 3
`
`
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`iii
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`
`EXHIBIT LIST
`
`EXHIBIT
`
`DESCRIPTION
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`1012
`
`1013
`
`U.S. Patent No. 9,299,467
`
`Complaint, Bracco Diagnostics Inc. v. Jubilant DraxImage
`Inc., Case No. 3-18-cv-04422 (D.N.J.)
`
`Complaint, In the Matter of Certain Strontium-Rubidium
`Radioisotope Infusion Systems, and Components Thereof
`Including Generators, Inv. No. 337-TA 3303 (U.S. I.T.C.)
`
`Order Granting Joint Motion to Stay Pending Resolution of ITC
`Proceedings (D.I. 9) Case No. 3-18-cv-04422 (D.N.J.)
`
`Waiver of Service, Bracco Diagnostics Inc. v. Jubilant
`DraxImage Inc.
`
`Prosecution History, U.S. application s.n. 12/137,356
`
`Prosecution History, U.S. application s.n. 12/137,377
`
`Prosecution History, U.S. application s.n. 12/137,363
`
`Prosecution History, U.S. application s.n. 12/137,364
`
`Prosecution History, U.S. application s.n. 12/808,467
`
`Prosecution History, U.S. application s.n. 14/455,623
`
`strontium-82/rubidium-82
`Alvarez-Diez, “Manufacture of
`generators and quality control of rubidium-82 chloride for
`myocardial perfusion imaging in patients using positron
`emission tomography,” Applied Radiation and Isotopes, v. 50,
`pp. 1015-23 (1999)
`
`Klein et al, “Precision Control of Eluted Activity from a Sr/Rb
`Generator for Cardiac Positron Emission Technology,” Engr. in
`Med. and Biology Soc. 26th Annual International Conference
`of the IEEE, vol. 1, pp. 1393-1396 (2004)
`
`
`
`iv
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`

`

`EXHIBIT
`
`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`DESCRIPTION
`
`Ran Klein, “Precise 82Rb Infusion System for Cardiac
`Perfusion Measurement Using 3D Positron Emission
`Tomography,” Ottawa-Carleton Institute for Electrical and
`Computer Engineering (Feb. 2005)
`
`Declaration of Robert T. Stone, Ph.D.
`
`Curriculum Vitae of Robert T. Stone, Ph.D.
`
`Declaration of Ventakesh Murthy, M.D.
`
`Barker, et al., U.S. Patent 4,585,009, granted April 29, 1986
`
`U.S. Pharmacopeia 23 National Formulary 18 (1995)
`
`Declaration of Andy Adler, Ph.D.
`
`Bracco CardioGen-82® Infusion System User’s Guide, Rev. 07
`(July 20, 2004)
`
`Tate, et al., U.S. Patent Publication No. 2008/0177126, filed
`October 31, 2007 and published July 24, 2008
`
`ISO 13485:2003 – Medical Devices – Quality Management
`Systems – Requirements for Regulatory Purposes (July, 2003)
`
`21 CFR Part 820.1 (2005)
`
`Chatal, et al., “Story of rubidium-82 and advantages for
`myocardial perfusion PET Imaging,” Frontiers in Medicine, v.
`2, art. 65, pp. 1-7 (Sept. 11, 2015)
`
`Bracco CardioGen-82® Rubidium Rb 82 Generator, Rev. 43-
`8200 (May 2000)
`
`10 CFR Part 20 (10 CFR 20.1001-2)
`
`10 CFR Part 20 (10 CFR 20.1003)
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`DESCRIPTION
`
`EN 62274:2005 – Medical Electrical Equipment – Safety of
`Radiotherapy Record and Verify Systems (December 28, 2005)
`
`The Chemical Rubber Co., Handbook of Radioactive Nuclides,
`Yen Wang ed., 1969
`
`to
`Inc.’s Responses
`Complainant Bracco Diagnostics
`Respondent’s Fourth Set of Interrogatories (No. 68), In the
`Matter of Certain Strontium-Rubidium Radioisotope Infusion
`Systems, and Components Thereof Including Generators, Inv.
`No. 337-TA 3303 (U.S. I.T.C.)
`
`Declaration of Carol Wadke
`
`deKemp, U.S. Patent Publication No. 2007/0213848
`
`deKemp U.S. Patent Publication No. 2007/0140958
`
`EXHIBIT
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`
`
`vi
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`
`I.
`
`INTRODUCTION
`Jubilant DraxImage Inc. (“Petitioner”) requests inter partes review of claims
`
`1-4, 6-16, and 18-22 (the “Challenged Claims”) of U.S. Patent No. 9,299,467 (“the
`
`’467 Patent,” Ex. 1001). This Petition establishes that the Challenged Claims are
`
`invalid over prior art cited in this Petition.
`
`The ’467 Patent is directed to computer- computer-controlled safety systems
`
`for radiopharmaceuticals.
`
` Ex. 1001, Abstract, 1:23-26.
`
` This
`
`includes
`
`“breakthrough testing” of a sample of radioactive eluate to determine if strontium
`
`in the eluate presents a medical risk, and preventing patient infusions, if so. Id., at
`
`17:33-61.
`
`It was a standard medical practice, for almost twenty years leading up to
`
`June 2008 (the earliest date to which the ’467 Patent claims priority), to perform
`
`breakthrough testing and to prevent patient infusions when problems were
`
`detected. Such procedures were performed manually, however, not by a computer.
`
`By 2008, automated breakthrough tests were taught by prior art. Therefore, the
`
`Challenged Claims are invalid.
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`II. MANDATORY NOTICES PURSUANT TO 37 C.F.R. § 42.8
`
`A. Real Parties-in-Interest (37 C.F.R. § 42.8(b)(1))
`The real parties-in-interest for this Petition are Jubilant DraxImage Inc.,
`
`Jubilant Pharma Limited, and Jubilant Life Science Limited.
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`The Patent Owner presently asserts the ’467 Patent in 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
`
`involving related patents. Exs. 1002, 1003, 1004. The district court case would be
`
`affected by a decision in this inter partes review
`
`Petitioner is concurrently filing petitions for IPR of U.S. Patent No.
`
`9,299,468 (“the ’468 Patent”), which have been assigned Case No. IPR2018-
`
`01448 and IPR2018-01450. The ’467 Patent and the ’468 Patent both claim
`
`priority to common applications.
`
`C. Lead and Backup Counsel and Service Information (37 C.F.R.
`§§ 42.8(b)(3)-(4))
`Robert L. Hails (Reg. No. 39,702) (lead counsel)
`T. Cy Walker (Reg. No. 52,337) (backup counsel)
`Baker Hostetler LLP
`1050 Connecticut Ave., N.W. Suite 1100
`Washington, DC 20036-5304
`Tel. 202.861.1500 | Fax. 202.861.1783
`rhails@bakerlaw.com | cwalker@bakerlaw.com
`
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`Theresa M. Weisenberger (Reg. No. 65,559) (backup counsel)
`Baker Hostetler LLP
`1170 Peachtree St. Suite 2400
`Atlanta, GA 30309-7676
`Tel. 404.459.0050 | Fax. 404.459.5734
`tweisenberger@bakerlaw.com
`
`
`Service Information: Please address all correspondence to lead counsel.
`
`Petitioner consents to e-mail service at Jubilant-Baker@bakerlaw.com.
`
`III. 37 C.F.R. §§ 42.103, 42.104 REQUIREMENTS
`A.
`Payment of Fees
`The PTO is authorized to charge Deposit Account No. 23-3050 for all fees
`
`associated with this Petition, including all fees set forth in 37 CFR § 42.15(a).
`
`B. Grounds for Standing (37 C.F.R. § 42.104(a))
`Petitioner certifies that the ’467 Patent is eligible for IPR and that no Real
`
`Party-in-Interest is barred from requesting inter partes review of the Challenged
`
`Claims. A complaint asserting infringement of the ’467 Patent was filed on March
`
`27, 2018. Ex. 1002. The Real Parties-in-Interest waived service effective June 1,
`
`2018, less than one year before the filing of this Petition. Ex. 1005. No Real
`
`Party-in-Interest has initiated a civil action challenging the validity of the ’467
`
`Patent.
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`
`IV. THE ’467 PATENT
`A.
`Summary of the ’467 Patent
`The ’467 Patent is directed to computer-controlled safety systems for
`
`radioactive materials, specifically radioisotope generators. Ex. 1001, at 23:48-64.
`
`The infusion system creates a rubidium-82 eluate by passing saline through a
`
`strontium generator 21 (red dashed lines). The eluate may be infused to a patient
`
`via patient line 305P, or it may be diverted to a waste bottle 23 via line 305W. Id.,
`
`at 4:59-5:9.
`
`’467 Patent (Ex. 1001), FIG. 1D
`The ’467 Patent discloses two types of breakthrough tests: one manual and
`
`
`
`one computer-controlled. During the manual test, a user collects a sample of
`
`rubidium eluate in a vial (not shown), transfers the vial to an external dose
`
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`calibrator, and measures activity of the sample twice: at the time of elution, and 60
`
`minutes thereafter. Id., at 17:9-18:4. The user enters measured activity values into
`
`a touch screen computer 17 (green), from which strontium breakthrough values are
`
`calculated. Id., at 18:7-24. For the computerized test, the strontium breakthrough
`
`testing is automated by an on-board dose calibrator (not shown) that is
`
`electronically coupled to computer 17. Id., at 18:48-63. In either case, if the
`
`breakthrough test results exceed an allowable limit, the system prevents patient
`
`infusions. Id., at 17:54-61.
`
`
`
`’467 Patent (Ex. 1001), FIGS. 1A, 1B, 2A
`Computer control is performed by a touchscreen computer 17 (green) and a
`
`
`
`controller (not shown). Touchscreen computer 17 is mounted on a cart shell 13
`
`(yellow) by a post. The controller is mounted within an interior space of the shell
`
`13, id., at 3:29-41, and accessed through a panel 174 on a rear of the shell. Id., at
`
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`4:13-16, FIG. 1B. Shell 13 also encloses a shielding assembly 200 (red) that
`
`includes compartments for the generator 21 and the waste bottle 23. Id., at 9:43-
`
`10:29.
`
`B.
`Prosecution History
`The ’467 Patent was filed as U.S.S.N. 14/455,623 (“the ’623 Application”)
`
`on August 8, 2014. The ’623 Application is a continuation of U.S.S.N. 12/808,467
`
`(“the ’467 Application”), filed as Application No. PCT/US09/47031 on June 11,
`
`2009, which is identified as a continuation of U.S.S.N. 12/137,356 (“the ’356
`
`Application”); 12/137,377 (“the ’377 Application”); 12/137,363 (“the ’363
`
`Application”); and 12/137,364 (“the ’364 Application”), all of which were filed
`
`June 11, 2008.
`
`1.
`The Prior Applications
`The prosecution histories of the applications to which the ’623 Application
`
`claims priority are extensive and, generally, they are not relevant to the Challenged
`
`Claims. For completeness, a short summary is presented below.
`
`During prosecution of the ’356 Application, the Examiner rejected certain
`
`claim limitations regarding a shielding assembly including a plurality of
`
`compartments, each with doors, as disclosed by U.S. Patent Publication No.
`
`20080177126 (“Tate,” Ex. 1022). Ex. 1006, at 132-143. Applicants traversed the
`
`specifics of this rejection that turned on specific components of Tate not disclosing
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`certain shielding components not at issue in the ’467 Patent claims (like doors on a
`
`plurality of compartments of the shielding assembly). Id., at 86-94. In their
`
`traversal, Applicants suggested that Tate does disclose radioactive shielding
`
`compartments. Id.
`
`Prosecution of the ’356, ’377, ’363, ’364, and ’467 applications involved
`
`issues that are not relevant to the Challenged Claims or the Grounds of the instant
`
`Petition. The ’356 Application claimed a shielding assembly including a plurality
`
`of compartments, each with doors. Ex. 1006, at 132-143, 86-93. The ’377
`
`Application claimed a cabinet structure for housing an infusion system that
`
`included
`
`separate
`
`radiation-shielded compartments
`
`for different
`
`system
`
`components. Ex. 1007, at 918-924. The ’363 Application claimed a disposable
`
`tubing circuit. Ex. 1008, at 1535-1541, 327-337, 36--39, 28. The ’364 Application
`
`and the ’467 Application claimed infusion systems and methods for operating
`
`them, and address claim elements describing elapsed time since elution complete,
`
`which does not appear in the Challenged Claims. See, e.g., Ex. 1009, at 2531-38,
`
`1117-21, 1108-11, 1091-1093, 1099-1111, 870-78, 861-64, 694, 664--73, 476,
`
`391-404, 358-73, 292-300, 223-34, 163-76, 51-60, 22-23; Ex. 1010, at 2427-36,
`
`929-931, 907--15, 838-45, 483-89, 377-89, 309-17, 249-57, 168-83, 51-52, 12-13.
`
`Their prosecution has little impact on the Challenged Claims.
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`
`2.
`The ’623 Application
`The Patent Office rejected most of the originally filed claims as obvious
`
`over different combinations of deKemp ’848, U.S. Publ’n. 2007/0213848 (Ex.
`
`1033), deKemp ’958, U.S. Publ’n. 2007/0140958 (Ex. 1034), and Hirschman (Ex.
`
`1022). Ex. 1011, at 201, 206. Applicants argued that deKemp ’848 and deKemp
`
`’958 did not disclose a “computer carried by a shielding assembly” or that the
`
`computer is configured to “receive activity data from the dose calibrator and
`
`calculate breakthrough test results.” Ex. 1011, at 145. Applicants amended the
`
`independent claims to require the computer [be configured to] “prevent[] a patient
`
`infusion procedure if a breakthrough test result exceeds an allowable limit.” Id., at
`
`158, 140-43.
`
`In the second Office Action, the Examiner rejected all but one of these
`
`amended claims as obvious either 1) over Hirschman, Alvarez-Diez (Ex. 1012),
`
`and Klein, “Precision Control of Eluted Activity from a Sr/Rb Generator for
`
`Cardiac Positron Emission Technology” (“Klein-2,” Ex. 1013), or 2) over
`
`Hirschman, Alvarez-Diez, Klein-2 and further in view of Tate. Ex. 1011, at 111-
`
`123. Specifically, the Examiner argued that Klein-2 provided evidence of the
`
`undesirable effects of exposing a patient to strontium as a result of continuing with
`
`a patient infusion when the breakthrough test results exceed an allowable limit.
`
`Id., at 114 (citing Klein-2 at 1396).
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`In response, Applicants did not dispute that the prior art taught a system
`
`including a shielding assembly, a computer carried by the cabinet structure, or a
`
`dose calibrator electronically coupled to the computer. Instead, Applicants simply
`
`argued the cited references did not disclose that the computer is carried by the
`
`cabinet structure, or that the computer is configured to prevent a patient infusion
`
`procedure if a breakthrough test result exceeds an allowable limit. Id., at 86-87,
`
`78.
`
`The Examiner allowed the claims, noting that the prior art does disclose all
`
`of the limitations of the independent claims “except that the computer is
`
`configured to prevent, or prevents, a patient infusion procedure if the breakthrough
`
`test result exceeds an allowable threshold.” Id., at 57-58. On that basis, a Notice
`
`of Allowance was issued. Id., at 35-38, 10.
`
`3.
`New Question of Patentability
`Although the Office considered the references relied upon in this Petition
`
`during original prosecution, this Petition presents new questions of patentability
`
`that the Office did not consider. Notably, the primary reference in this Petition—
`
`Ran Klein, “Precise 82Rb Infusion System for Cardiac Perfusion Measurement
`
`Using 3D Positron Emission Tomography,” (“Klein,” Ex. 1014)—which is relied
`
`upon as disclosing the one independent claim limitation the Examiner could not
`
`find in the prior art, was never substantively addressed during the prosecution of
`
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`the ’467 Patent. Respectfully, the Petitioners submit that the Examiner erred by
`
`failing to recognize that all of the limitations of the claims were known in the prior
`
`art. Had the Examiner correctly identified that this one limitation was expressly
`
`disclosed in Klein, Petitioners submit that the Patent Office would have found the
`
`Challenged Claims obvious over the prior art.
`
`Klein (Ex. 1014) has far better disclosure than the references cited during
`
`prosecution. See §§VII.A, VIII; Ex. 1015, §IX.B. Although Klein-2, deKemp
`
`’848, and deKemp ’958 refer to undesirable effects of strontium breakthrough,
`
`none discloses a computer to test for such issues or to implement safety protocols
`
`when detected. (Ex. 1013, 1033, 1034). Alvarez-Diez describes that a generator is
`
`connected to a delivery system only after initial quality control is finalized. Ex
`
`1012, at 1020. Thus, the Office has not considered the patentability issues
`
`presented in the instant Petition.
`
`V. LEVEL OF SKILL IN THE ART
`A person having ordinary skill in the art at the time of the alleged invention
`
`(“POSITA”) has a graduate’s degree with some emphasis in equipment design,
`
`automation, or controls, such as electrical engineering, systems engineering,
`
`mechanical engineering, or a related field, or an undergraduate degree in such
`
`fields with two to three years’ work experience in radioactive protection systems or
`
`
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`in medical device product, automation, or
`
`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`instrumentation design and
`
`development, including work with prototypes and finished commercial products.
`
`See Ex. 1015, §IV. Such a person would have had a basic understanding, through
`
`education or experience, of general design control principles and processes and
`
`practices for partial or full automation of existing processes or test procedures. See
`
`Id.
`
`Dr. Stone, whose curriculum vitae is attached (Ex. 1016), is an electrical
`
`engineer with a Ph.D., 14 years of experience working with safety systems for
`
`nuclear reactors and more than 35 years of experience working on medical devices
`
`and electronics. Ex. 1015, §I. Thus, he is qualified as at least a POSITA.
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`For related patents in the ITC case, Patent Owner has taken the position that
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`a POSITA has a graduate degree in medicine and/or in a medical related science,
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`and would have had some clinical, research and/or design experience with PET
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`imaging and/or PET imaging systems. Ex. 1031. This definition is flawed. See,
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`Ex. 1015, §IV. The Challenged Claims differ from Patent Owner’s predecessor
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`product (Ex. 1021) primarily through the addition of a computer to automate
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`strontium breakthrough testing procedures; medical personnel performed those
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`tests manually in Patent Owner’s prior product. Klein (Ex. 1014) possesses the
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`computer that Patent Owner’s product lacks; it differs from the Challenged Claims
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`based on the locations of the eluate reservoir (dose calibrator) and its shielding.
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`Medical personnel like those suggested by the Patent Owner lack the education and
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`experience to develop the hardware and software controls for such computer-
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`controlled systems or to design radiation shielding. Petitioner’s definition of the
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`POSITA should be adopted because it accounts for such issues.
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`VI. CLAIM CONSTRUCTIONS
`In an IPR, a claim is given its “broadest reasonable construction in light of
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`the specification of the patent in which it appears.” 37 CFR § 42.100(b). In
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`applying a broadest reasonable construction, claim terms generally are given their
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`ordinary and customary meaning, as would be understood by a POSITA in the
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`context of the entire disclosure. See In re Translogic Tech., Inc., 504 F.3d 1249,
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`1257 (Fed. Cir. 2007). Ex. 1015, §V. All claim terms have been assigned their
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`ordinary and customary meaning in this analysis.1
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`VII. SUMMARY OF THE PRIOR ART
`The medical aspects of rubidium-82, and its associated risks, were well
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`known long before June 2008, the earliest priority date claimed by the ’467 Patent.
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`1 If the Patent Office were to adopt the same claim construction standard as used in
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`district court proceedings, the analysis would remain the same. Ex. 1015, §V; see
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`83 FR 21221 (May 9, 2018).
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`See, e.g., Exs. 1017, at 7-9; 1012, at 1015; 1018, at 2:25-43; 1019, at 1392; 1025 at
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`1. Rubidium-82 is a radioactive medicine that permits measurement of blood flow
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`to patient tissues. Ex. 1017, at 7-8.
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`Rubidium-82 has a half-life of 76 seconds. Exs. 1014, at 7; 1012, at 1015;
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`1018, at 2:6-8; 1019, at 1392. Rubidium-82 is the byproduct of strontium-82 (82Sr)
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`decay. Ex. 1014, at 8. When an eluant, such as 0.9% NaCl saline, is flushed
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`through an “82Sr/82Rb generator,” the rubidium-82 is eluted in the form of 82RbCl
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`(eluate) that can be infused into a patient. Exs. 1014, at 8; 1012, at 1018, 1021;
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`1018, at 3:34-42; 1019, at 1392. The infusion process must occur quickly once the
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`rubidium-82 eluate is generated, owing to rubidium-82’s short half-life. Exs. 1014,
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`at 7-8; 1019, at 2:18-21.
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`Strontium-82, however, has a half-life of 25 days. Exs. 1014, at 8; 1019, at
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`1392. If strontium-82 leaked from a generator and were infused into a patient—
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`called a strontium “breakthrough”—it would present a health risk. Ex. 1014, at 9;
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`see also Exs. 1012, at 1019; 1019, at 1392; 1026 at 9. Accordingly, by 2008, it
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`was standard medical practice to test generators manually, on a daily basis, to
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`ensure that they operated within predetermined breakthrough limits. See Exs.
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`1014, at 9-10; 1012, at 1019; 1026 at 9. If breakthrough events were detected,
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`patient infusions were suspended until the generator was replaced. Id.
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
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`A. Klein (Ex. 1014)
`Klein is a student thesis that describes a computer-controlled rubidium-82
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`infusion system that performs sophisticated elution procedures. Ex. 1014, at 1-2,
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`71-97. Although not his primary focus, Klein describes computerized strontium
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`breakthrough testing and controls. Id., at 17-27. Klein’s thesis focuses instead on
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`various elution profiles that achieve higher-precision infusions than were possible
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`with predecessor systems. Id., at Abstract, Ch. 4.
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`Shown below, Klein’s system includes a rubidium-82 generator (red), an
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`activity counter (purple), a dose calibrator (blue), and system valves (orange), all
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`operating under control of a computer (green). Id., at 19 (system “is based around
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`a PC which interfaces with the various sensors and actuators,” including
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`communicating with the “dose calibrator[,] which is used to monitor the process
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`and control the elution.”). The dose calibrator measures breakthrough activity of
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`eluate generated by the generator. Id., at 50. Once the breakthrough test
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`completes successfully, patient elutions are enabled until the end of each day. Id.,
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`at 18.
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`Inter Partes Review Case No. IPR2018-01449
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`Ex. 1014, FIG. 2-2
`“All the components are assembled in a stainless steel cart” (also red,
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`
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`below). Id., at FIG. 2-3. The cart contains various components that provide
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`radiation shielding including lead rings for the generator and waste bottle,
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`shielding around the activity counter, and a heavy plastic lid that covers most
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`tubing components. Id., at 23, 46. The cart carries the computer (green) that
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`controls the system, including the generator that generates the rubidium-82 eluate.
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`Id., at 8, 20. The computer is electrically coupled to an off-cart dose calibrator
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`(blue) that measures breakthrough activity of an eluate sample. Id., at 19, 23, 50.
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
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`Ex. 1014, FIG. 2-3
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`
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`Ex. 1014, FIG. 2-4
`The computer implements a daily protocol, “including a test of breakthrough
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`
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`activity,” Id., at 50, 55, to ensure that the breakthrough activity follows safety
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`guidelines. Id., at 33. The computer software calculates the breakthrough test
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`based on activity measured by the dose calibrator. Id., at 50-51. The computer
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`“must ensure that the protocol is followed” so that patient infusion “is enabled only
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`after the prerequisites have been completed successfully.” Id., at 44. While Klein
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
`describes automated controls to determine breakthrough activity test results, it
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`notes that measuring the activity using the dose calibrator was not fully automated.
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`Nevertheless, Klein still teaches a computerized process, noting that fully
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`automating this process was a “key requirement” for “reduc[ing] radiation
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`exposure to the technologists.” Id., at 26.
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`Klein was published by the “ProQuest Digital Dissertations and Theses”
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`service on January 26, 2007, when it made the thesis available to the public
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`through that service. Ex. 1032. Klein also was published on Internet websites,
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`beforehand. Dr. Andy Adler, Ran Klein’s thesis advisor, declares that he
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`published
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`Klein
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`on
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`his
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`publicly-available
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`website
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`at
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`http://www.site.uottawa.ca/~adler in 2005 and, again, in 2006. Ex. 1020, ¶4. He
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`declares further
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`that he republished Klein by September 25, 2006 at
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`http://www.sce.carleton.ca/faculty/adler when he relocated his website due to a
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`change in employment. His declaration is corroborated by Wayback Machine
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`captures of the two websites, dated July 3 and Sept. 25, 2006, respectively. Ex.
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`1020, attachments B & C. Through either source, Klein was made available so
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`ordinarily skilled people who exercise reasonable diligence to locate it, see Jazz
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`Pharma. Inc. v. Amneal Pharma. LLC, 2018 WL 3400764, *5 (Fed. Cir. 2018),
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`and it qualifies as § 102(b) prior art under any of these dates.
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`Inter Partes Review Case No. IPR2018-01449
`U.S. Patent No. 9,299,467
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`B.
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`
`Tate (Ex. 1022)
`Tate, a U.S. Patent Publication published on July 24, 2008 and filed
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`on October 31, 2007, also discloses a radiopharmaceutical infusion system for PET
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`procedures that is built into a cart. Ex. 1022, ¶¶2, 70. Tate’s cart (yellow)
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`possesses a shielded well 121 that accommodates an on board dose calibrator 160
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`(blue). Id., ¶¶ 79, 84.
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`Ex. 1022, Figs. 1C, 1D
`Tate desires to minimize radiation exposure of medical personnel. Id., ¶¶9-
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`
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`10, 73, 87. Tate’s cart, therefore, contains radiation shielding (in red, below) for a
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`radiopharmaceutical vial 902, dose calibrator 160, tubing, and waste bottle 224.
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`Id., ¶¶73, 79, 87. Tate’s cart carries a computer 5, 15 (in green, below) that
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`controls operation of the infusion system.
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`Inter Partes Review Case No. IPR2018-01449
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`Ex. 1022, FIGS. 1E, 1F
`C. Bracco Manual (Ex. 1021)
`The Bracco Manual is a user guide for a commercially-available rubidium-
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`
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`82 infusion system. Ex. 1021, at 1. The Bracco Manual, issued at least as early as
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`20