Japanese Patent office
`Trial Board
`Written Appeal Decision
`
`5. Patented Invention 1 [Claim 1]
`
`(5-1) Comparison between Patented Invention 1 of this case and the invention of
`the Exhibit 1 by Party A
`(a)[Surgery [(b) [excitation light, [(c) an excitation light source mounted on a halogen
`lamp with a bandpass filter, [(d) [excorporeal, [(e) [near-infrared fluorescence excitation
`light from the pigment that is generated by excitation light, [(f) [a CCD camera having a
`TV lens mounted thereon with a sharp-cut filter for selecting only the fluorescence from
`the pigment, [(g) [imaging, [(h) [near-infrared fluorescence image, [and (i) [near-infrared
`fluorescence excitation light] in the invention of Exhibit 1 by Party A
`Correspond to
`(a) [surgery (b) [a first radiation that excites a fluorescent pigment, [(c) [an irradiation
`means, [(d) [externally to the patient body, [(e) [a second radiation emitted by the
`fluorescent pigment, [(f) [camera, (g) [visualizing, [(h) [contrast image, [and (i) [a
`radiation outside the visible spectrum] respectively, in Patented Invention 1 of this case.
`
`Also, [the flow of an in vivo liquid medium (such as blood or spinal fluid) [in the
`invention of Exhibit 1 by Party A and [blood flow [in Patented Invention 1 of this case are
`shared in that they both are [a flow of an in vivo liquid medium]
`
`Also, [anear-infrared fluorescence tracer comprising a complex (ICG-tfDL) of
`indocyanine green (ICG) of a near-infrared area fluorescence pigment and human high
`density lipoprotein (HDL)] in the invention of Exhibit 1 by Party A and [ICG [in
`Patented Invention 1 of this case are shared in that they both are [an infrared fluorescence
`tracer being carried in the flow of an in vivo liquid medium]
`
`Further, in the invention of Exhibit 1 by Party A. the detection is carried out after exposure for
`a predetermined time by a CCD camera and the signal from the CCD camera is subjected to
`data-processing with an image-processing device to achieve imaging; and in Patented
`Invention 1 of the case, the contrast image of th e coronary artery bypass is obtained at a rate of at
`least 15 images per second. They both are shared in that the contrast images of the target to be
`observed are obtained at a predetermined rate.
`
`Still further, by [wave front[in Patented Invention 1 of this case, Patented Invention 1 of the case
`defines it as [visualizing the movement of a fluorescent pigment being carried in the blood flow
`in a coronary artery bypass graft]. In addition, at [0071] of the Patent Specification of this case,
`there is described [The saline was used to flush in the line and to ensure passage of a complete
`a bolus through the femoral vasculature, producing a sharp wave front]. Judging from the fact
`that the wave front is formed as a result of the passage of a bolus, the [wave front]in Patented
`Invention 1 of this case is recognized as being [a boundary area moving with time, said boundary
`1
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`area being between the blood containing ICG and the blood containing no ICG]. On the other
`hand, in the invention of Exhibit 1 by Party A, the time-dependent observation is targeted at
`the location of and a change in concentration of the near-infrared fluorescent tracer that is
`moving in the living body by virtue of the flow of the in vivo liquid medium (such as blood or
`spinal fluid). While infrared fluorescence is emitted from the area of the in vivo liquid medium
`containing the infrared fluorescence tracer, the infrared fluorescence is not emitted from the area
`of the in vivo liquid medium not containing the infrared fluorescence tracer. It is thus understood
`that these situations of radiations will be visualized. And at the time, in order for the location
`and concentration change of the near-infrared fluorescence tracer to be observed in a time-
`dependent manner, it is evident that the observation is made on a boundary area moving with
`time, said boundary area being between the in vivo liquid medium that contains ICG and the in
`vivo liquid medium that does not contain ICG. Therefore, commonality exists between
`[observing the location of and a change in concentration of the near-infrared fluorescent tracer
`that is moving in the living body by virtue of the flow of the in vivo liquid medium (such as
`blood or spinal fluid) in a time-dependent manner [in the invention of Exhibit 1 by Party A and
`[the wave front formed by the blood containing ICG is visualized [in Patented Invention of this
`case, in regard to [visualizing the wave front formed by the flow of an in vivo liquid medium
`containing a near-infrared fluorescence tracer]
`
`Thus, it is acknowledged that both correspond to each other with respect to:
`[A device for visualizing the flow of a near-infrared fluorescence tracer being carried in the
`flow of an in vivo liquid medium during surgery, the device comprising:
`an irradiation means for emitting a first radiation that excites the tracer; and
`a camera for detecting a second radiation emitted by the tracer, to obtain a contrast image;
`wherein the irradiation means and the camera are located externally to the patient body; the
`wavelengths of the first and second radiations are within the band regions of excitation and
`emission spectra for use with the tracer; and the camera is capable of visualizing as a
`viewable image the radiation outside the visible spectrum and obtains the contrast image of
`the target of observation at a predetermined imaging rate, whereby a wave front formed by
`the flow of the in vivo liquid medium containing the tracer is visualized];
`
`but that they differ from each other with respect to the points below.
`
`(Difference point 1)
`Wfrile the tracer in the flow of the in vivo liquid medium in Patented Invention 1 of this case is ICG, it
`is an ICG-HDL complex in the invention of Exhibit 1 by Party A.
`
`(Difference point 2)
`In Patented Invention 1 of this case, the flow of the in vivo liquid medium in which the tracer
`moves by being carried is a blood flow in a coronary artery bypass graft. On the other hand,
`the blood flow in the coronary artery bypass graft is not described in Exhibit 1 by Party A
`although blood is illustrated as the in vivo liquid medium.
`
`2
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`(Difference point 3)
`With respect to the predetermined imaging rate at which the contrast images of the target of
`observation are obtained, contrast images are obtained at a rate of at least 15 images per
`second in Patented Invention 1 of this case. On the other hand, acquisition of contrast images at a
`rate of [at least 15 images per second is not described although exposure times of one second
`and eight seconds are illustrated in the invention of Exhibit 1 by Party A.
`
`(5-2) Judgment cnPatented Invention 1 of this case by this Board
`The aforementioned difference points will be studied,
`
`(Concerning the difference point 1)
`It is a well-known technology that a fluorescence imaging device using ICG as the near-
`infrared fluorescence tracer is used to carryout angiography (see the technologies of Exhibit
`1 by Party A and 6 by Party A). On the other hand, as to the Exhibit 1 by Party A in
`addition to disclosing that ICG-HDL complex is used as a near infrared ray fluorescent tracer to
`eliminate the restriction of the optimum site which is limited in angiography using ICG single
`body, since it cannot be affirmed that the excorporeal fluorescence imaging device described in
`Exhibit 1 by Party A has a one and inseparable configuration with ICG-HDL which cannot
`detect anything other than the infrared rays from the ICG-HDL, it is obvious to the person
`skilled in the art, who has been exposed to the invention of the Exhibit 1 by Party A that
`either of ICG or ICG-HDL is arbitrarily used as the infrared fluorescence tracer at the site of
`application which has thus far been unrestricted. Therefore, as to the angiography to which ICG
`has conventionally been applicable, ICG, which is well known in fluorescence imaging
`devices, may be employed instead of the ICG-HDL complex as the infrared fluorescence tracer
`in the invention of Exhibit 1 by Party A : it is merely a design matter that the person skilled in
`the art can appropriately perform.
`
`(Concerning Difference points 2 and 3)
`Judging from the fact that the invention of Exhibit 1 by Party A is an excorporeal
`fluorescence imaging device for use during surgery, it is evident that the invention places into
`the visual field the views of the surgery that, as the target for which the excorporeal fluorescence
`imaging device is used, whose observation is made on the flow of a fluorescent pigment
`being carried in an in vivo liquid medium.
`Further, during coronary artery bypass surgery, that the surgery during which the flow of
`a fluorescent pigment being carried in a blood flow in a coronary artery bypass graft is
`observed (i.e., during the coronary artery bypass surgery) is well known (see the technologies o f
`Exhibit 1 by Party A and 7 by Party A and 8 by Party A8). In addition, the Exhibit 1
`by Party A illustrates a flow of blood as the flow of an in vivo liquid medium in which the
`tracer moves, and also describes angiography using the ICG single entity as the prior art at
`[0007] and [0041). Furthermore, as stated as described above, if it is based on the design
`matter by the person skilled in the art as to which of the ICG-HDL complex or the well-
`known ICG is to be used as the infrared fluorescence tracer, the person skilled in the art can
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`easily conceive that the surgery for which the invention of Exhibit 1 by Party A is applied is
`decided to be the aforementioned well-known surgery during which the flow of the
`fluorescent pigment being carried in the blood flow in the coronary artery bypass is observed,
`and that the well-known ICG is used as the tracer so that the flow of the fluorescent pigment
`being carried in the blood flow in the coronary artery bypass may be observed.
`Then, at the time, when fluorescence imaging is conducted on a target that is different from
`that in the embodiment described in Exhibit lby Party A, the device will be used under
`observation conditions that correspond to the target in question, which is merely a matter that
`the person skilled in the art appropriately selects. If based on the three points below, the person
`skilled in the art can appropriately achieve to adjust the working speed to a rate of at least 15
`images per second at which the contrast images of the coronary artery bypass are acquired.
`
`(1) It is a well-known technology that in a fluorescence imaging device for visualizing
`fluorescence from ICG in a blood flow, a boundary area moving with time, said boundary area
`between the blood containing ICG and the blood containing no ICG is acquired as images at a
`rate of at least 15 pieces per second (see the technologies of Exhibit 5 by Party A Party A and
`6 by Party A)
`
`(2) A CCD camera C2400-75i (manufactured by Hamamatsu Photonics Co. Ltd.) used in the
`Embodiment of Exhibit 1 by Party A, v i e w e d from Exhibit 9 by Party A technology,
`is synchronized with the NTSC system capable of obtaining 30 pieces per second, and by using
`together with an image-processing device ARGUS20 used in the Embodiment of E x h i b i t 1
`by Party A, it is a CCD camera for fluorescence observation capable of improving low contrast
`images as more viewable ones by contrast enhancement or image intensification. Furthermore,
`according to technological matters of Exhibit 16 by Party A, 17 by Party A, 26 by Party A
`and 27 by Party A, its use in combination with the image-processing device ARGUS20 allows
`for visualization of the flow of ICG being carried in the blood flow in CABG at even an image
`acquisition rate of at least 15 pieces per second.
`Specifically, according to the Exhibit 3 by Party B it is reported that the SPY system,
`which is claimed to be the device involving the Patented Invention 1 of this case by the
`Demandee, displays a control brightness of 190 with an exposure time of 66 milliseconds, a
`device that simulates the device of E x h i b i t 1 by Party A is reported to display a control
`brightness of 10 with an exposure time of 66 milliseconds. Here in the exhibit 3 by party B, the
`device that simulates the device of Exhibit lby Party A has its image acquisition rate
`enhanced to at least 15 images/sec and its integration mode released (Demandee's Written
`Statement (Second) dated March 12, 2008, page 4, lines 17-22.) and it is not described
`that adjustment of gain in camera sensitivity has been carried out, in view of these, it is
`recognized that gain adjustment of camera sensitivity was not performed in the Exhibit 3 by
`Party B. Moreover,
`
`If based on the test result that the device that simulates the device in the aforementioned Exhibit 1
`by Party A displayed a control brightness of 10 with an exposure time of 66 milliseconds,
`
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`and in accordance with the Exhibit 26 by Party A and 27 by Party A, even in case the
`system of CCD camera 2400-75i and the image -processing device A R G U S 20 can
`acquire distinguishable images even if the brightness has been multiplied 3 0 times,
`identifiable images can be obtained, hence it is recognized that said system can visualize
`images with a brightness of 300 exceeding that of 190 displayed by the SPY device in the
`Exhibit 3 by Party B (the device that simulates of the Exhibit 1 by Party A that has been
`reported inthe Exhibit lby Exhibit 3 by Party B obtains the brightness of 10x30 at the
`image acquisition rate of 15 images per second) And, it is recognized that any target of
`observation which the SPY system can visualize may be similarly visualized.
`
`(3) When a device is used to observe fluorescence from a tracer that has been already known
`to fluoresce, the person skilled in the art normally carries out adjustment until the fluorescence,
`which should be emitted, can be viewed.
`
`Moreover, the operation effects of Patented Invention 1 of this case are within the range that the
`person skilled in the art can predict based on the invention of the Exhibit lby Party A and
`the aforementioned well-known technologies.
`
`Accordingly, the person skilled in the art could have easily conceived Patented Invention 1
`of this case based on the invention of Exhibit 1 by Party A and the aforementioned well-known
`technologies.
`
`6. Assertions by the Demandee
`
`Concerning Invalidation Reason 1, the Demandee asserts that none of the Exhibit 1 by Party A
`discloses the device of Patented Invention 1 of this case, there is no motivation to replace the
`invention described in Exhibit 1 by Party A into the like of Patented Invention 1 of this case,
`and also there are blocking factors and that the invention described in Exhibit 1 by Party A
`does not attain the invention that negates the progressiveness of Patented Invention 1 Thus,
`these points will be studied, (note by translator: the phrasing is not clear)
`
`(6-1) WrittenReply document dated October22, 2007 page 15 to 51
`(6-1-a) Regarding [The person skilled in the art in connection with the Patented
`Invention of the case [(the WrittenReply page 15 to 51
`
`The technology level by the person skilled in the art before the priority date of the Patent
`Application of this case will be assessed. First, the Patent Specification of this case describes,
`[ICG is preferred because it is readily available, and has long been approved for administration
`to humans for ophthalmic angiography, cardiac heart beat analysis and other indications] at
`[0039]. In addition, it is well known that indocyanine green is used for patients with cardiac
`disorders, as is shown in the technologies of Exhibit 1 by Party A, 28 by Party A, 29 by Party
`A and Stephan A. May [Photonic Approaches to Bum Diagnostics, [Bio photonics
`International, May/June, 1995, in the year of 1995, pp. 44-50 (which will be referred to as
`
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`[Well-Known Reference example 1 [hereafter), rindocyanine green (IG) has been used for
`more than 30 years for measuring the blood flow of the heart and liverl at page 46, the right
`column, lines 3-6, and [Standard doses of IG used in cardiology, for instance, are about 2 mg/kg
`of body weight] at page 48, the right column, lines 31-33, and it is also well known regarding
`the description as follows: that the range of application includes the blood flow in CABG, as
`judged from the technologies of the Exhibit 1 by Party, 28 by Party A and 2 9 by Party
`A, as well as the descriptions of Alberto Benchimol, et al. [Assessment of aortocoronary
`saphenous vein bypass function utilizing selection indicator dilution curves[American Heart
`Journal, Vol. 87, No 3, 1974, pp. 350-358 (which will be referred to as [Well-known Reference
`Example 2 hereafter); [We describe here the use of selective graft dilution curves as a method
`for assessing aortocoronary bypass function] at page 350, the left column, lines 9-11, [Cardio
`green indicator (indocyanine green, 3.1 mg), was injected by hand using a recalibrated pigment-
`dilution tube connected to a syringe containing 5 percent dextrose in water] at page 351, the
`left column, lines 30-33, and [Aortocoronary saphenous graft junction was evaluated in 21
`postoperative patients using the selective indocyanine green indicator dilution method] at page
`357, the left column, lines 2-5. Accordingly, it is recognized that indocyanine green is a
`pigment well known to the person skilled in the art, who is interested in CABG, as one used
`to observe the cardiac blood flow.
`Further, in the technical field of the fluorescence imaging devices using ICG to which the
`invention of Exhibit 1 by Party A as described above, pertains, the scope of the targets of
`application is as shown in the technologies of the Exhibit 1 by Party A, 5 by Party A,
`6 by Party A and 2 5 by Party A and is widely applied to the eye, gastrointestinal
`tract, ovary, bladder, blood vessels, liver, spleen, lymph nodes, and tumors, and there is no
`reason to be found that the cardiac blood vessels are the difficult target of observation to be
`applied. Therefore, there is no reason to conclude that the person skilled in the art, who is
`interested in CABG, must regard the fluorescence imaging device using ICG such as the
`invention of Exhibit 1 by Party A as the technology unrelated to CABG.
`Furthermore, it is well known that the cardiac vessels as the aforementioned blood vessels are
`included in the target to which the fluorescence imaging device using ICG is applied
`[W098/30144 (JP-2001-505472-T) (which will be referred to as [Well-Known Reference
`example 3hereafter] at page 2, lines 1-8, [Because systems for PRM (percutaneous myocardial
`revascularization) known in the art do not give any indication of whether the energy pulse
`has successfully generated a channel in the myocardium, it is difficult or impossible for an
`interventional cardiologist to detect and correct such a failure during the procedure]; at page 4,
`lines 21-23, [fluorescing contrast agents, known in the art, such as fluorescence or indocyanine
`green (ICG), may be injected into the blood stream to facilitate photo-detection of local blood
`perfusion by angiography]; at page 12, lines 1-11, [Fig. 7B schematically illustrates a catheter
`96, similar in design and function to catheter 90 described above, in accordance with another
`embodiment of the present invention. Sensor 42 of catheter 96 includes an optical sensor
`assembly 102, comprising a waveguide 98, which is connected to radiation source 61 (shown in
`Fig. 2A) and transmits fluorescence-stimulating radiation t o the myocardial tissue through a
`
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`lens 100. Assembly 102 further comprises a light detector 104, connected via wires 40 to
`circuit 44. Detector 104 receives fluorescent radiation emitted from the tissue and generates
`signals in response thereto. For embodiment, the detector may detect near-IR fluorescence of
`ICG injected into the patient’s blood stream and conveyed thereby to
`micro vasculature 94, as described in the above-mentioned article by May. Preferably, detector
`104 includes an optical filter, as known in the art, so that the detector receives radiation only in a
`wavelength band of interest]; Figs. 5 and 7; and Masaaki Sato et al., [Development o f a
`visualization metho d for microcirculations deep in organs using an in vivo infrared microscope
`system, [Report of the Medical Science Applied Research Foundation, 1990, December 20,
`1991, Vol. 9, pp. 63-73 (which will be referred to as [Well-Known Reference example 4
`(hereafter). [Nowadays, it has become necessary to directly observe the micro circulations of a
`parenchyma organ, such as a heart, liver and kidney, in realtime using the in vivo
`microscopy and to correlate them with various pathologies for examination] at page 63, the left
`column, lines 2-5; [It is also thought that ICG is applied to the measurement of plasma velocities.
`As Fig. 13 shows, when the flow of ICG intravenously administered is monitored with lapse of
`time, ICG first appears in arteriolas at the lower part of the picture and then after some time
`appears in venules at the upper part of the picture. According to this method, the plasma
`velocity in the arteriolas at the lower part of the picture has been calculated to be about 0.7
`mm/sec], at page 69, the right column, line 3 to page 70, the left column, line 2 (see Figs. 7
`and 13). In view of these, the person skilled in the art, who is interested in CABG, has no
`reason to regard the angiography with the fluorescence imaging device using ICG as being
`unknown.
`
`(6-1-b) [Each Exhibit 1 by Party A only represents a mere aggregation of
`technologies] (the Written Reply pp 18-19)
`
`As indicated in [(5-2) as described above, Judgment on Patented Invention 1 of this case by this
`Board] as described above, Patented Invention 1 of this case could have been easily conceived by
`the person skilled in the art based on the invention of Exhibit 1 by Party A and the
`aforementioned well-known technologies. A plurality of well-known technologies can support
`the technology standard as described above of the person skilled in the art around the time of
`filing the Patent Application.
`
`(6-1-c) [All of each Exhibit 1 by Party A relating to coronary artery surgeries
`deviate from the Patented Invention of this case [(the Written Reply pp 19-22)
`
`The technologies of Exhibit 1 by Party A, 7 by Party A and 8 by Party A show an
`embodiment of the surgery where observation is made on the flow of a fluorescent pigment
`being carried in the blood flow in a coronary artery bypass during coronary artery bypass
`surgery. Thus, the person skilled in the art, who has been exposed to the invention of
`Exhibit 1 by Party A, has no reason that he must think of excluding the aforementioned
`surgery from the surgeries where observations are made on the flows of fluorescent pigments
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`being carried in in vivo liquid media for which the invention at issue may target as its
`specific applications. The technologies o f Exhibit 1 by Party A, 7 by Party A and 8 by Party A
`can provide the motivations towards the Patented Invention of this case in the sense that they
`suggest to the person skilled in the art the well-known embodiments which can be added to
`the selection of targets of application by the invention of Exhibit 1 by Party A.
`
`(6-1-d) [None of Exh ib it 1 by Party A can be a reasonable starting point of the
`Patented Invention of the case] (the Written Reply pp 23- 28)
`
`The scope of the target of application by the fluorescence imaging device using ICG is as
`shown in the technologies of the Exhibit 1 by Party A,5 by Party A, 6 by Party A and
`2 5 by Party A and is widely applied to the eye, gastrointestinal tract, ovary, bladder, blood
`vessels, liver, spleen, lymph nodes, and tumors. Further, it is also well known that cardiac
`vessels as the aforementioned blood vessels are included for the application target for which
`the fluorescence imaging device using ICG is applied. There is no reason to conclude that the
`person skilled in the art, who is interested in CABG, must regard the fluorescence imaging
`device using ICG such as the invention of Exhibit 1 by Party A as the technology unrelated to
`CABG.
`
`(6-1-e) [The inventions involving the independent claims 1 and 11]
`(6-1-e-a) [None of Exhibit 1 by Party A discloses a device capable of visualizing the
`wave front of a coronary artery bypass graft such as that taught by the Patented
`Invention of this case] (Written Reply pp 28-42)
`
`As indicated in [(5-2) Judgment on Patented Invention 1 of this case by this Board] a s
`described above, it is recognized that the CCD camera C2400-75i used in the
`Embodiment of E x h i b i t 1 by Party A when used together with the image-processing
`device ARGUS20, is a CCD camera for fluorescence observation capable of improving low
`contrast images as more viewable ones by contrast enhancement or image intensification, said
`camera being able to obtain distinguishable images of the ICG wave front by CABG even at an
`image acquisition rate of 15 pieces per second through a 30-fold sensitivity increasing
`function.
`Moreover, although the Embodiment of Exhibit 1 by Party A is an example of observation of
`the rat spinal fluid flow, there is no description indicating that fluorescence imaging must
`be conducted under the same conditions in all the cases of targets to be observed. In performing
`the fluorescence imaging, observation conditions such as the settings of the CCD camera and
`the image-processing device, the concentration of ICG and the light source are adjusted in
`accordance with the target to be observed: it is merely a matter that the person skilled in the
`art appropriately selects.
`
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`(6-1-e-b) [There is no literature that discloses a device for an adequate irradiation means to
`excite the ICG pigment so that the wave front c an be visualized in CABG surgery] (The
`Written Reply pp 42- 48)
`The light source to be used in the Embodiment of Exhibit 1 by Party A excites the ICG
`pigment so that wave front can be visualized according to the invention of Exhibit 1 by
`Party A . Further, the technologies of Exhibit 1 by Party A, 21 by Party A, and 25 by Party A
`illustrate that there are a variety of light sources available for use in the fluorescence imaging
`device using ICG. Furthermore, as the irradiation dose of a laser that excites a fluorescent
`substance is adjusted in the technology of Exhibit 1 by Party A, observation conditions such as
`the settings of the CCD camera and the image-processing device, the concentration of ICG,
`and the adequate light source are chosen in accordance with the target to be observed when
`performing the fluorescence imaging: it is merely a matter that the person skilled in the art
`appropriately selects.
`
`(6-1-e-c) [There is no literature that discloses a device having mechanical
`characteristics adapted to be used in CABG] (The Written Reply pp 48-50)
`
`As indicated in (6-1-e-a) and (6-1-e-b) as described above, the invention of Exhibit 1 by Party A is
`a device having mechanical characteristics that can be used in CABG; and there is no reason to
`conclude that said device is unsuitable for use in CABG.
`
`(6-2) Written statement dated January 15, 2008 (pp 2-4)
`Concerning [ Supplemental assertion that Exhibit 1 by Party A contains blocking factors]
`
`There are the extraction description in [n] a s described above [ICG fluorescence arises
`from pigment molecules bound to blood proteins in the moving blood volume];
`
`The description in the Exhibit 12 by Party B, translation page 1 line 11-13 that are amended by 1
`of the Exhibit 12 by Party B [indocyanine green bound extensively to plasma proteins and
`fluoresced with the excitation condition attained, and emission maxima being near the near
`infrared part of the spectrum]; the description in the well-known reference example 4 the page
`63 right column line 8-13 [Indocyanine green (ICG) is a pigment of the tricarbocyanine type
`with a molecular weight of 775 (Fig. I)6 and is a diagnostic agent that is used in clinical
`medicines and is non-toxic to the living body. It has been chiefly used to evaluate the liver
`and circulatory functions. This agent, being quickly bound to plasma proteins in blood7),
`is metabolized in the liver and excreted into the bile juice.6) [In consideration of these
`descriptions, the fluorescent pigment (ICG) in Patented Invention 1 of the case is believed to
`bind to plasma proteins when it is carried in the blood flow in the coronary artery bypass graft.
`On the other hand, as is pointed out in [g], [HDL is a protein in blood; and as is pointed out in
`[h] as described above, an ICG aqueous solution and HDL are stirred to prepare an ICG-HDL
`complex. There is no reason to conclude that a marked difference should result compared to the
`state of the ICG-HDL complex being carried in a blood flow. In this perspective, based on the
`
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`premise that ICG has the function of being excited by the first radiation and emitting the second
`radiation in the state where it is carried in blood, it will be possible to judge that there is no
`substantial difference between ICG and the ICG-HDL complex. Hence, as indicated in [(5-2)
`Judgment on Patented Invention 1 of this case by this Board [as described above,
`concerning the difference pointl in [(5-1) Comparison between Patented Invention 1 of this case
`and the invention of Exhibit 1 by Party A 1 [as described above, it can be said that whether to
`use ICG-HDL or ICG as the infrared fluorescence tracer for the site of application to which
`ICG has been conventionally available is a matter that the person skilled in the art can
`appropriately determine.
`
`(6-3) Written Reply document (Second) dated February 29, 2008
`(6-3-1) Concerning [Validity of Exhibit 1 by Party A as the primary embodiment]
`
`As indicated in [(5-2) Judgment on Patented Invention 1 of this case by this Board [as described
`above, Patented Invention 1 of the case could have easily been conceived by the person skilled
`in the art based on the invention of Exhibit 1 by Party A and the aforementioned well-known
`technologies. Also, as indicated in (6-1-a), there is no reason to conclude that the person skilled
`in the art, who is interested in CABG, would not refer to Exhibit 1 by Party A for anything in
`light of the technology level before the priority date of the Patent Application of the case,
`
`(6-3-2) Concerning [Fluorescent pigments in Exhibit 1 by Party A] (pp 4-5)
`
`As indicated in (6-2) described above whether to use ICG-HDL or ICG as the infrared
`fluorescence tracer for the site of application for which ICG has been conventionally available
`is a matter that the person skilled in the art can appropriately determine.
`
`(6-3-3) Concerning [Camera and image-processing system of Exhibit 1 by Party A] etc.
`(PP 5-13)
`As indicated in [(5-2) Judgment on Patented Invention 1 of the case by this Board] as
`described above, it is recognized that the system of C2400-75i+ARGUS20 is capable of
`visualizing the flow of ICG being carried in the blood flow in CABG similarly to the SPY
`device.
`
`Further, although the Embodiment of Exhibit 1 by Party A is an embodiment of observation
`of the rat spinal fluid flow, there is no description indicating that fluorescence imaging must be
`conducted under the same conditions in all the cases of targets to be observed. In performing
`the fluorescence imaging, observation conditions such as the settings of the CCD camera and
`the image-processing device, the concentration of ICG and the light source are adjusted in
`accordance with the target to be observed: it is merely a matter that the person skilled in the
`art appropriately selects.
`
`Furthermore, although each camera of the C4880 series is described in the column of [the
`maximum frame rate ] at page 23 of Exhibit 15 by Party B the upper limit for the system of
`
`10
`
` VI