Filed on behalf of Visionsense Corp.
`
`By: Joseph M. Casino, Reg. No. 57,224
`Wiggin and Dana LLP
`450 Lexington Avenue
`Suite 3800
`New York, New York 10017
`Tel: (212)551-2842
`Email: JCasino@wiggin.com
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`VISIONSENSE CORP.
`
`Petitioner,
`
`v.
`
`Patent Owner of
`
`U.S. Patent No. 8,892,190 to
`
`IPR Trial No. TBD
`
`PETITION FOR INTER PARTES REVIEW OF
`
`U.S. Patent No. 8,892,190
`
`UNDER 35 U.S.C. § 312 AND 37 C.F.R. § 42.104
`
`
`
`By: Joseph M. Casino, Reg. No. 57,224
`Wiggin and Dana LLP
`450 Lexington Avenue
`Suite 3800
`New York, New York 10017
`Tel: (212)551-2842
`Email: JCasino@wiggin.com
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`VISIONSENSE CORP.
`
`Petitioner,
`
`v.
`
`Patent Owner of
`
`U.S. Patent No. 8,892,190 to
`
`IPR Trial No. TBD
`
`PETITION FOR INTER PARTES REVIEW OF
`
`U.S. Patent No. 8,892,190
`
`UNDER 35 U.S.C. § 312 AND 37 C.F.R. § 42.104
`
`
`
`1002
`
`1003
`
`1004
`
`Exhibit Description
`U.S. Patent No. 8,892,190. “Method and apparatus
`1001
`for performing intra-operative angiography,” filed
`March 13, 2012.
`Little, John R., et al. “Superficial temporal artery to
`middle cerebral artery anastomosis: intraoperative
`evaluation by fluorescein angiography and xenon-
`133 clearance.” Journal of neurosurgery 50.5
`(1979): 560-569.
`U.S. Patent 6,3 51,663. “Methods for diagnosing
`and treating conditions associated with abnormal
`vasculature using fluorescent dye angiography and
`dye-enhanced photocoagulation,” filed September
`10, 1999.
`Japanese Laid Open Patent Publication No. H9-
`309845 (Translation). “NEAR-INLRED
`FLUORESCENT TRACER AND FLUORESCENE
`IMAGING METHOD,” filed May 21, 1996.
`U.S. Patent No. 5,394,199. “Methods and apparatus
`for improved visualization of choroidal blood flow
`and aberrant vascular structures in the eye using
`fluorescent dye angiography,” filed May 17, 1993.
`Specification of Argus 20 with C2400-75i, dated
`May 1997
`Goldstein et al., “Intraoperative Angiography to
`Assess Graft Patency After Minimally Invasive
`Coronary Bypass,” Ann Thorax Surg, 66: 1978-
`1982, (1998).
`Eren, Serdar, et al. “Assessment of microcirculation
`of an axial skin flap using indocyanine green
`fluorescence angiography.” Plastic and
`reconstructive surgery 96.7 (1995): 1636-1649
`Decision of European Patent Office Technical
`Board of Appeal revoking Counterpart Patent No.
`1143852
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`Abbreviation
`‘190 Patent
`
`Little
`
`Flower I
`
`Jibu
`
`Flower II
`
`Argus 20
`Specification
`Goldstein
`
`Eren
`
`EPO Decision
`
`Exhibits
`
`2
`
`
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`Translation of Decision of Japanese Patent Office
`Trial Board revoking Counterpart Patent No. Patent
`No. 3,881,550
`Summary of Invention Submitted to EPO
`
`Novadaq 510K showing X-Ray Fluoroscopy as
`Predicate Device
`Takayama et al., Intraoperative Coronary
`Angiography Using Fluorescein, Ann Thorac Surg.
`51:140-143 (1991)
`Hyvarinen, Lea and Robert W. Flower.
`“Indocyanine green fluorescence
`angiography.” Acta ophthalmological 58.4 (1980):
`528-538
`The Sony U-Matic Videocassette Recorder
`
`Joseph, et al. “Evaluation of the circulation of
`reconstructive flaps using laser-induced
`fluorescence of indocyanine green.” Annals of
`plastic surgery 42.3 (March 1999): 266-274.
`
`JPO Decision
`
`Invention
`Summary
`51 OK
`
`Takayama
`
`Hyvarinen
`
`Sony U-Matic
`
`Joseph
`
`3
`
`
`
`Table of Challenged Claims
`
`Abbreviation
`Vessel Graft Preamble
`
`Administering Step
`
`Illuminating Step
`
`Wavefront Capturing Step
`
`Claim Limitations
`1. A method for assessing blood
`flow moving through a vessel graft
`anastomosed in fluid
`communication with an
`interconnected group of blood
`vessels in an animal, the vessel graft
`and at least a portion of the blood
`vessels being exposed during a
`surgical procedure on the animal,
`the method comprising the steps of:
`(a) administering a fluorescent dye
`to the animal such that the dye
`enters the vessel graft and the
`interconnected group of blood
`vessels;
`(b) exciting the fluorescent dye
`within the vessel graft and said
`exposed portion of the
`interconnected group of blood
`vessels with a source of
`illumination, thus causing the dye to
`emit radiation;
`(c) capturing the radiation emitted
`by the fluorescent dye with a
`camera capable of imaging a series
`of angiographic images within the
`vessel graft and said exposed
`portion of the interconnected group
`of blood vessels, the images
`including at least an image of a
`fluorescent wavefront
`corresponding to an interface
`between the flowing blood that first
`contains the fluorescent dye
`introduced, such image being
`captured by the camera as the
`fluorescent wavefront transitions
`
`4
`
`
`
`Evaluation Step
`
`Modifying Step
`
`Vessel Graft Preamble
`
`Administering Step
`
`Illuminating Step
`
`800-850 Wavelength Requirement
`
`15 Images/Second Requirement
`
`Wavefront Capture Step
`
`through the exposed vessel graft and
`interconnected croup of blood
`vessels; and
`(d) evaluating the angiographic
`images to assess blood flow through
`the vessel graft relative to blood
`flow through the interconnected
`group of blood vessels.
`2. The method of claim 1, further
`comprising:
`modifying said anastomosed vessel
`graft based on results of said
`evaluating step, thereby improving
`resultant blood flow through said
`vessel graft.
`3. A method for assessing blood
`flow moving through an vessel graft
`in an animal, the vessel graft being
`exposed during a surgical procedure
`on the animal, comprising the steps
`of:
`(a) administering a fluorescent dye
`to the animal such that the dye
`enters the vessel graft;
`(b) exciting the fluorescent dye
`within the vessel graft with a source
`of illumination, thus causing the dye
`to emit radiation, the fluorescent
`dye having a peak absorption and
`emission in the range of 800 to 850
`nm;
`(c) capturing the radiation emitted
`by the fluorescent dye with a
`camera capable of imaging a series
`of angiographic images of the vessel
`graft at a rate of at least 15 images
`per second while the subject’s heart
`is beating, the images including at
`least an image of a fluorescent
`wavefront corresponding to an
`
`5
`
`
`
`interface between the flowing blood
`that first contains the fluorescent
`dye introduced, such image being
`captured by the camera as the
`fluorescent wavefront transitions
`through the exposed vessel graft;
`and
`(d) evaluating the angiographic
`images to assess blood flow through
`the vessel graft relative to blood
`flow through a group of blood
`vessels interconnected to the vessel
`graft.
`
`Evaluation Step
`
`6
`
`
`
`Visionsense Corp. (“Petitioner” or “Visionsense”) petitions for Inter
`
`Partes Review (“IPR”) under 35 U.S.C. §§ 311-319 and 37 C.F.R. § 42 of
`
`claims 1-3 (“the Challenged Claims”) of U.S. Patent No. 8,892,190 (“the
`
`‘190 patent”). As explained in this petition, and in the accompanying
`
`declaration of David J. Langer, M.D., Chief of Neurosurgery at Lenox Hill
`
`Hospital, New York, there exists a reasonable likelihood that Visionsense
`
`will prevail with respect to at least one of the Challenged Claims.
`
`The Challenged Claims are invalid based on teachings set forth in at
`
`least the references presented in this petition. Visionsense respectfully
`
`submits that an IPR should be instituted, and that the Challenged Claims
`
`should be canceled as being invalid.
`
`I. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8(A)(1)
`
`A. REAL PARTY-IN-INTEREST UNDER 37 C.F.R. § 42.8(B)(1)
`
`Petitioner, Visionsense Corp., is the real party-in-interest.
`
`B. RELATED MATTERS UNDER 37 C.F.R. § 42.8(B)(2)
`
`No litigation matters exist related to this proceeding.
`
`C. COUNSELUNDER 37 C.F.R. § 42.8(B)(3)
`BACKUP COUNSEL
`LEAD COUNSEL
`
`Joseph M. Casino, Reg. No. 57,224
`Wiggin and Dana LLP
`450 Lexington Avenue
`New York, NY 10017
`
`Abraham Kasdan, Reg. No. 32,997
`Wiggin and Dana LLP
`450 Lexington Avenue
`New York, NY 10017
`
`7
`
`
`
`T: 212-551-2841
`Email: jcasino@wiggin.com
`
`T: 212-551-2841
`Email: akasdan@wiggin.com
`
`D. SERVICE INFORMATIONUNDER 37 C.F.R. § 42.8(B)(4)
`
`Please address all correspondence and service to counsel at the
`
`address provided in Section 1(C). Petitioner also consents to electronic
`
`service by email at icasino@wiggin.com and akasdan@wiggin.com.
`
`II. CERTIFICATE OF GROUNDS FOR STANDING
`
`Petitioner certifies pursuant to Rule 42.104(a) that the patent for
`
`which review is sought is available for inter partes review and that
`
`Petitioner is not barred or estopped from requesting an inter partes review
`
`challenging the patent claims on the grounds identified in this Petition.
`
`III. OVERFIEW OF CHALLENGE AND RELIEF REQUESTED
`
`Pursuant to Rules 42.22(a)(1) and 42.104(b)(l)~(2), Petitioner requests
`
`that each Challenged Claim be cancelled.
`
`A. PRIOR ART PATENTS AND PRINTED PUBLICATIONS
`
`Petitioner relies on the Exhibits 1001 - 1008 and 1013 -1016 in the
`
`Table of Exhibits as prior art.
`
`B. GROUNDS OF CHALLENGE
`
`Petitioner requests cancellation of the Challenged Claims as
`
`unpatentable under (pre-AIA) 35U.S.C. §§ 102 and 103 on the following
`
`grounds:
`
`8
`
`
`
`Ground 1: Claims 1 and 2 are anticipated by Little
`
`Ground 2: Claims 1-3 are obvious in view of Little, Flower I and
`Flower II.
`
`Ground 3: Claims 1-3 are obvious in view of Flower I, Flower II and
`Little or Goldstein
`
`Ground 4: Claims 1-3 are obvious in view of Jibu, Flower II and Little
`or Goldstein
`
`IV. TECHNOLOGY BACKGROUND
`
`A. BRIEF DESCRIPTION AND SUMMARY OF CLAIMS 1-3
`
`The technology in this case relates to imaging blood flow by adding a
`
`fluorescent dye to the blood, exciting it with excitation light to emit
`
`fluorescence, and taking a video image using a CCD camera to visualize
`
`how the dye transitions through vessels. Claims 1-3 at issue (which
`
`constitute all claims of the c 190 Patent) are method claims that claim use of
`
`this well-known fluorescence imaging technique to analyze the patency (i.e.,
`
`degree of openness; the relative absence of blockage) of a vascular graft.
`
`All claims require a camera capable of capturing images of the “wavefront,”
`
`i.e. the boundary between fluorescent and non-fluorescent regions of the
`
`blood, where the fluorescent dye is first introduced. Claim 3 requires that
`
`the fluorescent dye have its peak absorption and emission spectrum in the
`
`range of 800-850 nm, which corresponds to that of the well-known dye,
`
`indocyanine green (ICG) (Ex. 1001, 14:29), and that the image capture rate
`
`9
`
`
`
`of the CCD camera be at least 15 images per second, which is what a
`
`conventional off the shelf CCD camera could obtain. (See Ex. 1011.)
`
`The prior art relied on herein shows that the equipment needed to
`
`perform the claimed methods was known in the prior art. The use of such
`
`methods to assess blood flow in grafts during surgery was also known and
`
`was an obvious way to use such equipment.
`
`Claim 1 ’s preamble (“Vessel Graft Preamble”) broadly sets the
`
`environment to view vessel grafts in an animal during surgery:
`
`“A method for assessing blood flow moving through a vessel graft
`
`anastomosed in fluid communication with an interconnected group of blood
`
`vessels in an animal, the vessel graft and at least a portion of the blood
`
`vessels being exposed during a surgical procedure on the animal, the method
`
`comprising the steps of:”
`
`Limitation (a) requires administering of a fluorescent dye so that it
`
`enters the vessel graft and related blood vessels (“the Administering Step”):
`
`“(a) administering a fluorescent dye to the animal such that the dye
`
`enters the vessel graft and the interconnected group of blood vessels;”
`
`Limitation (b) requires exciting the dye with a source of illumination,
`
`such as a laser, so that it emits fluorescence radiation (“the Illuminating
`
`Step”):
`
`10
`
`
`
`“(b) exciting the fluorescent dye within the vessel graft and said
`
`exposed portion of the interconnected group of blood vessels with a source
`
`of illumination, thus causing the dye to emit radiation;”
`
`Limitation (c) requires the capturing of a series of images of the
`
`fluorescent wavefront as it “transitions”, i.e., moves, through the graft and
`
`related blood vessels due to the blood flow, (“the Wavefront Capture Step”):
`
`“(c) capturing the radiation emitted by the fluorescent dye with a
`
`camera capable of imaging a series of angiographic images within the vessel
`
`graft and said exposed portion of the interconnected group of blood vessels,
`
`the images including at least an image of a fluorescent wavefront
`
`corresponding to an interface between the flowing blood that first contains
`
`the fluorescent dye introduced, such image being captured by the camera as
`
`the fluorescent wavefront transitions through the exposed vessel graft and
`
`interconnected group of blood vessels;”
`
`Finally, limitation (d) requires evaluation of those images to assess
`
`blood flow through the vessel graft (“the Evaluation Step”):
`
`(d) evaluating the angiographic images to assess blood flow through
`
`the vessel graft relative to blood flow through the interconnected group of
`
`blood vessels
`
`11
`
`
`
`Dependent Claim 2 adds the step of modifying the vessel graft based
`
`on the Evaluation Step (“the Modifying Step”):
`
`“modifying said anastomosed vessel graft based on results of said
`
`evaluating step, thereby improving resultant blood flow through said vessel
`
`graft.”
`
`Claim 3 is largely the same as Claim 1 but adds two additional details.
`
`First, it adds a requirement to the Administering Step that the fluorescent
`
`dye has “a peak absorption and emission in the range of 800 to 850 nm”
`
`(“the 800-850 Wavelength Requirement”). Second, it adds a requirement to
`
`the Wavefront Capture Step that the camera be capable of imaging “at least
`
`15 images per second while the subject's heart is beating,” (“the 15
`
`Image/Second Requirement”).
`
`B. OVERVIEW OF THE ’ 190 PATENT
`
`U.S. Patent No. 8,892,190 was filed on March 13, 2012 almost
`
`thirteen years after a provisional application was filed on September 24,
`
`1999. The sole figure shows the exemplary device proposed for looking at
`
`vessel grafts during an operation using fluorescence:
`
`12
`
`
`
`In the figure, a laser 1 is emits radiation through bandpass filter 5 and
`
`optics 7 using a wavelength that will illuminate a fluorescent dye injected
`
`into the tissues of interest 3 in a patient. The preferred dye injected into the
`
`tissue of interest 3 is ICG. CCD camera 2 captures the emissions from the
`
`dye and can be fitted with a bandpass filter 6, polarizing filter 14a and lens
`
`system 8. A distance detection system 9, 9a may be used. The camera 2 may
`
`relay the captured images to an analog-to-digital converter 10, PC 15 and
`
`monitor 11. A printer 13, VCR 13 and monitor 12 may also be used for
`
`recording, printing or playback.
`
`13
`
`
`
`During the course of the prosecution, the applicants were faced with
`
`several rejections due to Flower I in the parent and grandparent applications
`
`to the application issuing as the ‘190 Patent.
`
`First, in the grandparent application, the applicant received
`
`anticipation and obviousness rejections of the pending claims on the basis of
`
`Flower I and Flower I in view of certain other references. In its obviousness
`
`rejection, the examiner wrote:
`
`“Flower I discloses a method and diagnosis and treating conditions
`
`associated with abnormal vasculature using a fluorescent dye angiography . .
`
`. but fails to show explicitly a . . . bypass graft.” (Application No.
`
`09/744,034, Non-final Rejection dated Mar. 10, 2004.) However, a
`
`secondary reference, the examiner observed, showed a “coronary artery
`
`bypass grafting on a beating heart whereby an angiographic image is
`
`obtained before and after the invasive procedure.” {Id.) The examiner also
`
`observed that while Flower I did not show the use of a video monitor, a
`
`secondary reference disclosed a method of performing heart surgery using
`
`thermographic imaging that uses a plurality of images. {Id.) Among other
`
`things, the examiner also pointed to other secondary references that
`
`disclosed the use of CCD camera, in a relevant clinical setting. {Id.)
`
`14
`
`
`
`In response to the obviousness rejections, the applicants argued that
`
`there was insufficient motivation to apply Flower I to the intraoperative
`
`assessment of the patency of a coronary artery. (Application No. 09/744,034,
`
`Applicant Remarks, Feb. 14, 2005.) In addition, the applicants argued, while
`
`the prior art showed the capturing of before-and-after angiographic images,
`
`there was insufficient motivation to “record a dynamic event concurrent with
`
`surgery.” (Id.) The applicants also argued that there was insufficient
`
`motivation to combine Flower I with other prior art, including those that
`
`disclosed the use of a CCD camera. (Id.)
`
`In the only prior art rejection in the application leading to the ‘ 190
`
`Patent the applicants received an anticipation rejection on the basis of
`
`Takayama et al., Intraoperative Coronary Angiography Using Fluorescein,
`
`Ann Thorac Surg. 51:140-143 (1991) (“Takayama,” Ex. 1013). The
`
`examiner reasoned wrote that Takayama “discloses a method of assessing
`
`patency of a portion of a blood vessel included the steps of administering a
`
`fluorescent dye to an animal. . . obtaining at least one angiographic image of
`
`the vessel portion . . ., and evaluating the image to assess patency of the
`
`vessel portion.” (Application No. 13/419,368, Final Rejection, Conf. No.
`
`5106, Feb. 4, 2013.)
`
`15
`
`
`
`In response, the applicants argued that Takayama was not anticipatory
`
`because it did not disclose the use of a camera. For example, the applicants
`
`noted, Takayama is “directed to naked eye visualization . . . and, as such,
`
`does not disclose or suggest fluorescent dye imaging of moving blood
`
`through the vessel graft.... Therefore, there would be no need for a camera
`
`to obtain angiographic images of blood flow.” (Application No. 13/419,368,
`
`Applicant Remarks, Oct. 2, 2013.) The applicants’ arguments and certain
`
`amendments overcame the examiner’s rejections, and the patent ultimately
`
`issued.
`
`The Little reference, showing the use of fluorescent imaging to assess
`
`graft patency, was not reviewed by the patent examiner. The Jibu reference,
`
`which resulted in cancellation of parallel device claims in the Europe and
`
`Japan, was not used by the examiner. Further, and very significantly, the
`
`arguments made by applicant during prosecution about the relevance of
`
`Flower I were incomplete and misleading as the work by Flower I was
`
`crucial to the purported invention of applicant. As a result, while the Flower
`
`I reference was examined by the patent examiner, it was not reviewed in
`
`combination with Little or Jibu.
`
`16
`
`
`
`C. BACKGROUND TO THE INVENTION
`Despite having argued during prosecution of the ‘190 Patent that the
`
`Flower I reference was not relevant to the then-pending claims, the patent
`
`owner later revealed that the work by Flower was actually the linchpin of the
`
`purported invention. During proceedings in the Japanese Patent Office, the
`
`patent owner submitted a statement from one of the inventors describing the
`
`invention process. (Ex. 1011.) This summary describes that several of the
`
`inventors spent “a considerable amount of time trying to obtain fluorescence
`
`images of ICG.” (Id.) But they “were unable to observe any fluorescence.”
`
`(Id.) They studied “mainly Bob Flower’s publications” in the literature and
`
`wanted to bring Bob Flower to Winnipeg to help. (Id.) After getting
`
`funding for Flower to come to Winnipeg for “a weekend” he helped the
`
`inventors determine they should introduce “ICG as a bolus of higher
`
`concentration” and replace their $40K lab camera with “an $800 camera that
`
`acquired images at video rate i.e. 30 frames per second.” (Id.)
`
`After Flower’s visit, they acquired “very promising images of
`
`coronary arteries in the rat heart.” (Id.) The team then reached out to cardiac
`
`surgeon who tried and helped refine the equipment. (Id.)
`
`Curiously, and fatally, Flower (one of the named inventors on the
`
`‘190 Patent) had already filed patents that disclosed the use of fluorescence
`
`17
`
`
`
`imaging to evaluate blood flow using a CCD camera that could image 30
`
`frames a second before the provisional filing date of the ‘190 Patent.
`
`(Flower I and Flower II). Further, it was already well known that imaging,
`
`including fluorescence imaging, was useful to examine a graft during
`
`surgery so that revisions could be made to fix any blood flow issues in the
`
`graft. (Little and Goldstein). As the identified prior art demonstrates,
`
`Claims 1-3 cover nothing more than what was already known in the prior
`
`art.
`
`V. LEVEL OF ORDINARY SKILL IN THE ART
`
`The claims of the ‘190 Patent relate to the method of using fluorescent
`
`imaging to look at a vessel graft during surgery. A medical doctor with 2-3
`
`years’ experience using or designing imaging equipment for use during
`
`medical procedures would be one of ordinary skill in the art. (Declaration of
`
`David J. Langer, M.D., dated March 21, 2017 (“Langer Deck”) If 10.)
`
`VI. CLAIM CONSTRUCTION
`
`A. LEGAL PRINCIPLES
`
`During an inter partes review, claims are given the broadest
`
`reasonable construction. 37 C.F.R. § 42.100. “[Cjonstruing a patent claim
`
`according to its broadest reasonable construction helps to protect the public .
`
`. . [b]ecause an examiner’s (or reexaminer’s) use of the broadest reasonable
`
`18
`
`
`
`construction standard increases the possibility that the examiner will find the
`
`claim too broad (and deny it) . . . Cuozzo Speed Techs., LLC v. Lee, 136 S.
`
`Ct. 2131,2144-45 (2016).
`
`B. CLAIM CONSTRUCTION
`
`Under the broadest reasonable construction, there would appear to be
`
`no limiting construction of the claims that avoids the prior art. Petitioner
`
`reserves the right to respond to any claim construction arguments made by
`
`the patent owner. While the plain language of the claims appears
`
`understandable under the broadest reasonable construction, petitioner makes
`
`the following comments:
`
`• “Vessel graft” can be the graft of any vessels. It can be vessels
`
`in the leg, heart or brain. (‘190 Patent, 1:36-41.)
`
`• “Animal” can be a human or non-human animal. (‘190 Patent,
`
`4:15-17).
`
`• The amount of “fluorescent dye” is not limited as to minimum
`
`or maximum quantities in the Administering Step, nor is there
`
`any requirement that the dye be injected in a single
`
`administration (bolus) or in multiple successive administrations.
`
`19
`
`
`
`• The method of exciting the fluorescent dye is not limited in the
`
`Illuminating Step and may be done in any manner (e.g., laser,
`
`filtered broad-band light source, etc.).
`
`• The Modifying Step is not limited to a particular modification
`
`of the vessel graft.
`
`• Evaluation of blood flow through the vessel graft relative to
`
`interconnected vessels is not limited to numerical comparisons
`
`of fluorescence intensities in the vessel graft and connected
`
`vessels. Any type of comparison (e.g., fluorescence signal in
`
`the graft and no signal in the downstream vessels) would
`
`qualify as relative evaluation.
`
`VII. THE PRIMARY REFERENCES
`
`A. LITTLE (EX. 1002)
`
`Little is prior art under (pre-AIA) 35 U.S.C. § 102(b) based on its
`
`1979 publication date. Little describes a method for using fluorescent-dye
`
`angiography to assess blood flow intraoperatively, during an anastomosis
`
`(graft) of two cerebral arteries. (Little, Ex. 1002, 561-62.) In particular,
`
`Little describes administering the dye (sodium fluorescein) to the patient;
`
`exciting the dye ( with a strobe light to induce fluorescence); capturing
`
`multiple images of the resultant fluorescence in a manner that permits
`
`20
`
`
`
`observation of the changing interface between the fluorescing and non
`
`fluorescing portions of the vasculature (i.e., the dye wavefront; id. Figs. 1-3)
`
`as the dye flows through the vasculature; and evaluating the efficacy (in
`
`particular the patency) of the graft on the basis of the angiograms. {Id. at
`
`562.)
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`Little further discloses that where the angiogram shows an occlusion
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`in the graft, further surgical intervention may be carried out to improve
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`blood flow, and offers clinical examples of such modifications to the graft.
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`{Id. at 562.)
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`Little is relied on for Ground 1 (anticipation of Claims 1 and 2) and
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`for Grounds 2, 3, and 4 (obviousness of Claims 1, 2 and 3).
`
`B. FLOWER I (EX. 1003)
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`Flower I describes a variety of methods for using fluorescent dyes in
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`the treatment and observation of animal (including human) vasculature, and
`
`in particular vascular abnormalities. (Flower, I, Ex. 1003, 2:27-30; 10:8-19)
`
`The methods include techniques for enhancing the clarity of the fluorescent
`
`angiograms and observing the direction of the blood flow through the
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`vasculature. {Id. at 2:31-67.) Flower I discloses that the angiograms may be
`
`captured during surgery. {Id. at 9:23-26.)
`
`21
`
`
`
`Flower I recommends the use of the “readily available” dye ICG,
`
`which Flower I discloses as having its peak absorption and emission spectra
`
`in the range of 800-850 nm. (Id. at 5:41-55.) Flower I also describes the use
`
`of a CCD video camera to aid the visualization. (Id. at 1:42-47, 10:3-7.)
`
`Flower I observes that the disclosed methods permit observation of the
`
`wavefront of the dye as it transits through the blood vessels. (Id. at 4:36-46.)
`
`This petition cites Flower I for Grounds 2, 3, and 4 (obviousness as to
`
`Claims 1, 2 and 3). Flower I is prior art under (pre-AIA) 35 U.S.C. §
`
`102(e).1
`
`C. FLOWER II (EX. 1005)
`
`Flower II describes a method for generating ICG angiograms to show
`
`blood flow through aberrant blood vessels such as choroidal
`
`neovascularization in the eye. (Flower II, Ex. 1005 at 3:56-62.)
`
`Flower II recognizes the “obvious [ ]” utility of tracking a sharply-
`
`defined wavefront through the vascular network. (Id. at 2:40-42.) Flower II
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`1 To the extent that the patent owner argues Flower I can be removed as
`prior art through this will be disputed. Further, Flower II, prior art under 35
`U.S.C. § 102(b) has the same pertinent disclosure, i.e., the use of ICG dye,
`illumination with a laser with 805 nm range (see light source 44 at Flower II,
`Ex. 1005, 9:12), use a CCD camera 36 that captures at up to 29 frames a
`second (claim 5) and visualization of aberrant vascular structures (Abstract).
`
`22
`
`
`
`also discloses taking a sequence of angiograms “at high speeds (15-30
`
`images/second).” (Id. at 4:64-65.)
`
`This petition cites Flower II for Grounds 2, 3, and 4 (obviousness as
`
`to Claims 1, 2 and 3). Flower II is prior art under (pre-AIA) 35 U.S.C. §
`
`102(b).
`
`D. JIBU (EX. 1004)
`
`Jibu describes a method of administering fluorescent dye into a living
`
`body that is illuminated to cause it to fluoresce. (Jibu, Ex. 1004, 3). Jibu
`
`discloses the use of the dye during surgery. (Id. at 15.)
`
`Jibu describes detection of the fluorescence with a CCD camera
`
`(C24000-75i, manufactured by Hamamatsu Photonics K.K.) outfitted with
`
`an image processing device (Argus 20, manufactured by Hamamatsu
`
`Photonics K.K.) (Jibu, Ex. 1004, 13-14), a combination whose frame rate
`
`exceeds 15 images per second. (Ex. 1006; see also Ex. 1010, 5-6.)
`
`Jibu discloses ICG, a dye that fluoresces at a wavelength of at least
`
`700nm, but that is preferably 800 nm or higher, and describes one such dye
`
`(ICG) that fluoresces at 835 nm. (Jibu, Ex. 1004, 7-8, 13.)
`
`This petition cites Jibu for Ground 4 (obviousness as to Claims 1, 2
`
`and 3). Jibu, published December 2, 1997, is prior art under (pre-AIA) 35
`
`U.S.C. § 102(b).
`
`23
`
`
`
`Jibu was the main reference used in the successful oppositions to
`
`parallel device claims in Japan and Europe. (Exs. 1009 and 1010).
`
`The Japanese patent office observed that Jibu “illustrates a flow of
`
`blood as the flow of an in vivo liquid medium in which the tracer moves, as
`
`well as describes angiography using the ICG single entity as the prior art. . .
`
`.” (Ex. 1010, 4.) Therefore, the office concluded, “the person skilled in the
`
`art can easily conceive . . . the well-known ICG ... as the tracer so that the
`
`movement of the fluorescent dye being carried in the blood flow in the
`
`coronary artery bypass graft may be observed. {Id. at 5.)
`
`The Japanese patent office also concluded that camera, together with
`
`the image-processing device, disclosed in Jibu obtains the requisite
`
`brightness “at the image acquisition rate of 15 images per second.” {Id. at
`
`6.) In short, the Japanese patent office stated, “the person skilled in the art
`
`could have easily conceived [the device patent] based on [Jibu] and [other]
`
`well-known technologies.” {Id.)
`
`24
`
`
`
`The European Appeal Board likewise upheld the invalidation of the
`
`device patent on the basis of Jibu. Among other things, the European patent
`
`office stated that Jibu discloses that imaging “was performed in real time
`
`with an exposure time of one second . . . The imaging capabilities of [Jibu]
`
`is however not restricted to the particular use described in [Jibu].
`
`Consequently, when the device of [Jibu] is used for a different purpose, such
`
`the presently claimed imaging of the fluorescent dye carried in the
`
`bloodstream of a cardiovascular graft, the skilled person . . . will be able to
`
`obtain an image revealing the passage, i.e., the ‘movement’, of the
`
`fluorescent dye through the cardiovascular graft ‘during surgical procedure’
`
`and ‘while the heart is beating.’” (Ex. 1009, 21-22.)
`
`E. GOLDSTEIN (EX. 1007)
`
`Goldstein describes a method the use of intraoperative fluoroscopic
`
`angiography to assess a coronary artery bypass graft. (Goldstein, Ex. 1007,
`
`1979.) Goldstein touts the benefits of the intraoperative angiogram, which
`
`provides real-time imaging and thus permits “surgical revision” and optimal
`
`surgical result. {Id. at 1979; see also, e.g., id. at 1980 (“[I]ntrapoerative
`
`coronary angiography using a portable fluoroscopic system documents the
`
`immediate results of MINCAB [minimally invasive coronary artery bypass
`
`grafting] . . . and provides timely data that could influence intraoperative
`
`25
`
`
`
`treatment and patient outcome”).) Goldstein discloses the use of 30/frame
`
`per second fluoroscope. (Id. at 1979.)
`
`Goldstein is directly pertinent prior art as one using a more complex
`
`(x-ray based) fluoroscope during open heart surgery would consider simpler
`
`equipment shown in Flower I, Flower II or Jibu. (Langer Decl. If 33.) This
`
`is evidenced by Novadaq Technologies, Inc. the exclusive licensee of the
`
`patent owner’s own submissions to the Food and Drug Administration,
`
`which cites fluoroscopy equipment as a predicate device. (Ex. 1012).
`
`This petition cites Goldstein for Ground 3 (obviousness as to Claims
`
`1, 2 and 3). Goldstein is prior art under (pre-AIA) 35 U.S.C. § 102(b).
`
`VIII.
`
`SPECIFIC GROUNDS FOR PETITION
`
`A. Ground 1: Claims 1 and 2 are anticipated by Little
`
`The Vessel Graft Preamble of Claim 1 recites “[a] method for
`
`assessing blood flow moving through a vessel graft anastomosed in fluid
`
`communication with an interconnected group of blood vessels in an animal,
`
`the vessel graft and at least a portion of the blood vessels being exposed
`
`during a surgical procedure on the animal.” Assuming the preamble provides
`
`a claim limitation, it is disclosed by Little. Little describes “[fjluorescein
`
`angiography [that] provided an immediate assessment of anastomotic
`
`patency and clearly displayed the distribution of blood entering the
`
`26
`
`
`
`epicerebral circulation through” an artery. (Little, Ex. 1002, 560). In other
`
`words, Little discloses using a dye-fluorescence angiography procedure to
`
`intraoperatively evaluate blood flow through a graft. (Langer Decl. ^ 35.)
`
`Limitation (a), the Administering Step, describes “administering a
`
`fluorescent dye to the animal such that the dye enters the vessel graft and the
`
`interconnected group of blood vessels.” Little discloses this element.
`
`Recognizing that “[t]he technique of fluorescein angiography has been
`
`described in detail elsewhere,” Little discloses the use of fluorescein
`
`angiography “performed before and after anastomosis” by way of sodium
`
`fluorescein dye being “injected rapidly into the ipsilateral [common carotid
`
`artery] through the indwelling catheter.” (Little, Ex. 1002, 562.) Little thus
`
`discloses the administration of a fluorescent dye in a vessel graft. (Langer
`
`Decl. 37.)
`
`Element (b), the Illuminating Step, describes “exciting the
`
`fluorescent dye within the vessel graft and said exposed portion of the
`
`interconnected group of blood vessels with a source of illumination, thus
`
`causing the dye to emit radiation.” Little discloses this element as well,
`
`describing that “[i]illumination for photography was provided by a strobe
`
`light. . . [and] [b]arrier filters . . . were used to keep unwanted exciting
`
`radiation from reaching the film.” (Little, Ex. 1002, 562.) In other words,
`
`27
`
`
`
`the strobe light excites the fluorescein dye, which fluoresces in response.
`
`(Langer Decl. % 39.)
`
`Element (c), the Wavefront Capture Step, describes “capturing the
`
`radiation emitted by the fluorescent dye with a camera capable of im
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