DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant's arguments filed 01/29/2026 have been fully considered but they are not persuasive.
Applicant contends that “there is no aspect of Ho's device that requires a sensor provided on the device, nor is there any aspect of function of Ho's device that would be improved by the inclusion of such a sensor” since “Ho already incorporates a feedback loop that modulates the power output of the device based on backscattered harmonic signals that eliminates any need for such a sensor or localized monitoring.” Examiner respectfully disagrees.
In response to Applicant’s argument that Ho does not require a sensor, Examiner takes the position that “detect[ing] a radiofrequency signal backscattered from the implantable illumination device” implies a sensor in order to detect the backscattered radiofrequency, or light, signal (See Ho Abstract). Although a sensor is not explicitly claimed in Ho, this does not teach the exclusion of a sensor, especially since Ho discloses the detection of a radiofrequency signal.
Applicant contends that “paragraph [0008] of Emken cited by the Office, characterizes light reflecting from tissues as noise that pollutes measurement data that should be shielded against. Paragraphs [0061]-[0064] of Emken, which describe the construction of Emken's device, specifically reference an opaque membrane that performs this light-blocking function to block extraneous light and shield the indicator element 106. In other words, the only reference in Emken to light reflecting from tissues is a clear instruction that this phenomenon should not be measured, and thus Emken teaches away from the proposed combination … Regardless, Emken's device lacks any structures or sensors capable of measuring fluorescence from organs or tissues - Emken is specifically constructed to only measure (as is relevant here) light emitted from the indicator element 106, which is part of the sensor device.” Examiner respectfully disagrees.
In response to Applicant’s argument that “paragraph [0008] of Emken cited by the Office, characterizes light reflecting from tissues as noise that pollutes measurement data that should be shielded against. Paragraphs [0061]-[0064] of Emken, which describe the construction of Emken's device, specifically reference an opaque membrane that performs this light-blocking function to block extraneous light and shield the indicator element 106. In other words, the only reference in Emken to light reflecting from tissues is a clear instruction that this phenomenon should not be measured, and thus Emken teaches away from the proposed combination,” Examiner would like to note that the Non-Final Office Action dated 10/29/2025 utilizes multiple passages from Emken to teach the claimed “sensor configured to detect, in real time, activity data from a tissue cluster of an organ” and “detecting an auto-fluorescence value.” Specifically, Emken teaches a sensor, and the sensor detecting an auto-fluorescence value, explicitly in ¶[0030], where “The sensor 100 may be implanted, for example, in a living animal's arm, wrist, leg, abdomen, or other region of the living animal suitable for sensor implantation,” and ¶[0041], where “sensor 100 also includes one or more photodetectors 110 (e.g., photodiodes, phototransistors, photoresistors, or other photosensitive elements) which, in the case of a fluorescence-based sensor, is sensitive to fluorescent light emitted by the indicator molecules 104 such that a signal is generated by the photodetector 110 in response thereto that is indicative of the level of fluorescence of the indicator molecules and, thus, the amount of analyte of interest (e.g., glucose).” Examiner takes the position that Emken does not teach away from the proposed combination as Emken explicitly teaches one or more photodetectors, which are sensors, to measure fluorescent light emitted by the indicator molecules 104.
Additionally, in response to Applicant’s argument that “Emken's device lacks any structures or sensors capable of measuring fluorescence from organs or tissues - Emken is specifically constructed to only measure (as is relevant here) light emitted from the indicator element 106, which is part of the sensor device,” Examiner takes the position that Emken possesses structures or sensors capable of measuring fluorescence from organs or tissues. Emken teaches that the sensor can be implanted “in a living animal's arm, wrist, leg, abdomen, or other region of the living animal suitable for sensor implantation,” which implies implantation of the sensor in organs or tissues as claimed by Applicant. (See Emken ¶[0030]). Emken further teaches that “sensor 100 also includes one or more photodetectors 110 (e.g., photodiodes, phototransistors, photoresistors, or other photosensitive elements) which, in the case of a fluorescence-based sensor, is sensitive to fluorescent light emitted by the indicator molecules 104 such that a signal is generated by the photodetector 110 in response thereto that is indicative of the level of fluorescence of the indicator molecules and, thus, the amount of analyte of interest (e.g., glucose),” which does not teach only measuring light emitted from the indicator element 106 as Applicant claims since light generated from indicator molecules, which correspond to analytes of interest, is measured. (See Emken ¶[0041], emphasis added).
Applicant contends that “There is therefore no evidence, guidance, motivation, expectation of success, or the like on the record that might support the combination that the Office seeks to make here. The only source of such a motivation to combine or expectation of success would be Applicant's own specification. Accordingly, the specific modification of Ho with Emken proposed here by the Office can only be the result of improper hindsight reconstruction ... that the combinations of references proposed in the outstanding Action are improper and reflect the sort of indiscriminate picking and choosing of features from references without consideration of those references as a whole that is indicative of improper hindsight reconstruction.” Examiner respectfully disagrees.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Additionally, in response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Examiner takes the position that there is motivation to combine Ho with Emken in order to sense the concentration of analytes in tissue via in vivo detection (Emken ¶[0012]) and to communicate analyte concentrations with an external device and display the analyte concentrations to a user (Emken ¶[0036]).
Applicant contends that “The Office identifies various teachings in Schnermann that allegedly teach or suggest using fluorescence in response to an excitation light to detect the presence of ROS, but then the Office only broadly states that it would be obvious to combine these teachings with Ho and Emken … it is further unclear what benefit might be obtained by combining this detection with Ho’s device,” that “it is unclear if the Office is proposing to change the light sources of Ho out for the one discussed in Schnermann … adding an additional light source to Ho's device as allegedly guided by Schnermann … or some other change,” and that the “procedures in Schnermann are also primarily directed to detecting the presence of ROS, not the quantity of ROS as claimed.” Examiner respectfully disagrees.
In response to Applicant’s argument that “The Office identifies various teachings in Schnermann that allegedly teach or suggest using fluorescence in response to an excitation light to detect the presence of ROS, but then the Office only broadly states that it would be obvious to combine these teachings with Ho and Emken … it is further unclear what benefit might be obtained by combining this detection with Ho’s device,” Examiner notes the motivation as provided on page 10 of the Non-Final Office Action dated 10/29/2025, which describes the relevant motivation, and which states that it would be obvious to combine Schnermann with Ho as modified to determine a quantity of ROS “…since ROS have been implicated in a variety of inflammatory diseases, such as cancer and atherosclerosis (Schnermann ¶[0145]), and ROS detection can aid in the mitigation of disease.”
Regarding Applicant’s argument that “it is unclear if the Office is proposing to change the light sources of Ho out for the one discussed in Schnermann … adding an additional light source to Ho's device as allegedly guided by Schnermann … or some other change,” Examiner would like to clarify that Schnermann is utilized to teach that “the activity data comprises a quantity of reactive oxygen species of the organ determined by detecting an auto-fluorescence value from the tissue cluster of the organ from which the quantity of reactive oxygen species of the organ is determined,” specifically the detection of an auto-fluorescence value to determine a quantity of reactive oxygen species.
Additionally, in response to Applicant’s argument that the “procedures in Schnermann are also primarily directed to detecting the presence of ROS, not the quantity of ROS as claimed,” Examiner takes the position that Schnermann teaches detecting the quantity of ROS as claimed. Schnermann teaches determining a concentration of ROS in the sample, which is a quantity of ROS. (See Schnermann ¶[0145], emphasis added, where “ROS have been implicated in a variety of inflammatory diseases, such as cancer and atherosclerosis. ROS detection can be performed in vitro, ex vivo, or in vivo … ROS present in the sample may oxidize the compound to recreate the fluorophore, which is detected by any suitable method. Fluorescence indicates the presence of ROS in the sample. The intensity of the fluorescence may be correlated to the concentration of ROS in the sample”).
Applicant contends that “Denison is silent regarding the monitoring of fluorescence or auto-fluorescence from ROS to determine ROS quantities and/or using such detections as part of a control feedback loop. Indeed, none of the references on record teach or suggest such a scheme. Likewise, none of the references contain any teachings that would guide a person having ordinary skill in the art to a combination that would perform such a scheme absent Applicant's own specification.” Examiner respectfully disagrees.
In response to Applicant’s argument that “Denison is silent regarding the monitoring of fluorescence or auto-fluorescence from ROS to determine ROS quantities and/or using such detections as part of a control feedback loop. Indeed, none of the references on record teach or suggest such a scheme,” Examiner would like to note that Denison is utilized to teach a transceiver integrated into the wireless implanted device and that the processing unit is configured to update the stimulation parameters based on the activity data, where the combination of references teaches the monitoring of fluorescence or auto-fluorescence from ROS to determine ROS quantities and/or using such detections as part of a control feedback loop. In response to applicant's arguments against the references individually, here Denison, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Furthermore, in response to applicant’s argument that “none of the references contain any teachings that would guide a person having ordinary skill in the art to a combination that would perform such a scheme absent Applicant's own specification,” where there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, it would have been obvious to one of ordinary skill in the art at the time of invention to combine Denison with Ho as modified in order to allow for bi-directional communication between an implantable stimulator and the external device (Denison ¶[0114]), to record the effect of the performed optical stimulations, and to provide a feedback loop that allows for adjustments to the treatment parameters of subsequent optical stimulations (Denison ¶[0153]) that triggers initiation or adjustment of optical stimulation to alleviate patient symptoms (Denison ¶[0172]).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 4, 6-11, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over Ho et al. (hereinafter “Ho”) (U.S. Pub. No. 2021/0060350 A1) in view of Emken et al. (hereinafter “Emken”) (U.S. Pub. No. 2017/0049371 A1), Schnermann et al. (hereinafter “Schnermann”) (U.S. Pub. No. 2020/0179536 A1), and Denison et al. (hereinafter “Denison”) (WO 2011/066320 A2).
Regarding claim 1, Ho teaches a system comprising: an external device comprising a processing unit and a power supply (¶[0087], where “controller 1044 which in this implementation is a computer running LABVIEW software controls the signal generator 1032 to control the power.” Examiner takes the position that a computer is equivalent to an external processing unit and that a computer inherently incorporates a power supply.) configured to transmit stimulation parameters (¶[0088], where “the controller 1044 which determines the light dose and controls the power of the drive signal”);
a wireless implantable device (¶[0117], where “the wireless implantable illumination device 3110 is a thin, flexible device, which comprises mesh of light emitting diode”) comprising:
a stimulator including a plurality of light components corresponding to at least a first wavelength and a second wavelength (¶[0004], where “the light source comprises a first light emitting device configured to emit light having a first wavelength and a second light emitting device configured to emit light having a second wavelength different from the first wavelength”) and a flexible elastomer coupled to the plurality of light components (¶[0006], where “the implantable illumination device comprises a planar substrate and wherein the light source comprises a plurality of light emitting devices arranged on the planar substrate … planar substrate may be formed from a flexible material,” ¶[0118], where “substrate 3210 is formed from a flexible material such as polyimide.” Examiner takes the position that the flexible material is an elastomer since polyamide is a type of elastomer.), and
wherein the stimulator is configured to illuminate, based on the stimulation parameters (¶[0079], where “dosimetry module 1040 controls the light dose delivered to the target region … a prescribed light doing rate was established in two steps: (1) while holding the transmit power constant, the transmitter position was adjusted until the measured harmonic backscatter was maximized (compensating for potential misalignment between the transmitter and receiver); (2) while holding the transmitter position constant, the transmit power was tuned such that the light emission was set to the desired level using the dosimetry module 1040.” Examiner takes the position that by determining the light dose with a dosimetry model that the illumination parameters are determined and then applied.), one of the plurality of light components coupled to the flexible elastomer (¶[0004], where “the light source comprises a first light emitting device configured to emit light having a first wavelength and a second light emitting device configured to emit light having a second wavelength different from the first wavelength,” ¶[0006], where “the implantable illumination device comprises a planar substrate and wherein the light source comprises a plurality of light emitting devices arranged on the planar substrate”).
Although Ho teaches a wireless implantable device, Ho does not teach the wireless implantable device comprising a sensor configured to detect, in real time, activity data from a tissue cluster of an organ, wherein the activity data comprises a quantity of reactive oxygen species of the organ determined by detecting an auto-fluorescence value from the tissue cluster of the organ from which the quantity of reactive oxygen species of the organ is determined, nor a transceiver configured to transmit the activity data to the external device. Furthermore, although Ho teaches a processing unit, Ho does not teach that the processing unit is configured to update the stimulation parameters based on the activity data.
Emken teaches “a sensor that may be used to detect the presence, amount, and/or concentration of an analyte in a medium” (Abstract), where the “present invention relates generally to sensors for implantation or insertion within a living animal and measurement of a concentration of an analyte in a medium within the living animal” (¶[0003]) and that the sensor includes a light source, such as a light emitting diode (LED), that emits light over a range of wavelengths (¶[0040]), and further teaches a wireless implantable device (¶[0030], where “the sensor 100 is implanted in a living animal (e.g., a living human). The sensor 100 may be implanted, for example, in a living animal's arm, wrist, leg, abdomen, or other region of the living animal suitable for sensor implantation”) comprising:
a sensor configured to detect, in real time, activity data from a tissue cluster of an organ (¶[0005], where “sensor may include an indicator element … in an implantable fluorescence-based glucose sensor, fluorescent indicator molecules may reversibly bind glucose and, when illuminated with excitation light (e.g., light having a wavelength of approximately 378 nm), emit an amount of light (e.g., light in the range of 400 to 500 nm) that depends on whether glucose is bound to the indicator molecule,” ¶[0008], where “the light may be reflected by the tissue or may cause the tissue to fluoresce and return light at a different wavelength. The reflected and fluoresced light from the tissue may return through the indicator element or other transparent part of the sensor and may be received by one or more light detectors (e.g., photodiodes) of the sensor,” ¶[0030], where “The sensor 100 may be implanted, for example, in a living animal's arm, wrist, leg, abdomen, or other region of the living animal suitable for sensor implantation,” ¶[0041], where “sensor 100 also includes one or more photodetectors 110 (e.g., photodiodes, phototransistors, photoresistors, or other photosensitive elements) which, in the case of a fluorescence-based sensor, is sensitive to fluorescent light emitted by the indicator molecules 104 such that a signal is generated by the photodetector 110 in response thereto that is indicative of the level of fluorescence of the indicator molecules and, thus, the amount of analyte of interest (e.g., glucose).” Examiner takes the position that the measurement is in real-time since a signal is generated by the photodetector that is indicative of the level of fluorescence and since no delay is stated such that feedback is immediate. Additionally, Examiner takes the position that the sensor is capable of detecting activity data from a tissue cluster of an organ since the sensor detects fluoresced light from tissue and is implantable in any region suitable for sensor implantation, which includes organ tissue.), detecting an auto-fluorescence value (¶[0041], where “sensor 100 also includes one or more photodetectors 110 (e.g., photodiodes, phototransistors, photoresistors, or other photosensitive elements) which, in the case of a fluorescence-based sensor, is sensitive to fluorescent light emitted by the indicator molecules 104 such that a signal is generated by the photodetector 110 in response thereto that is indicative of the level of fluorescence of the indicator molecules and, thus, the amount of analyte of interest (e.g., glucose)”), and
an external transceiver configured to transmit the activity data to the external device (¶[0030], where “the system includes a sensor 100 and an external transceiver 101,” ¶[0031], where “transceiver 101 may be an electronic device that communicates with the sensor 100 to power the sensor 100 and/or obtain analyte (e.g., glucose) readings from the sensor 100,” ¶0036], where “transceiver 101 may communicate (e.g., using a wireless communication standard, such as, for example, Bluetooth) with a remote device (e.g., a smartphone, personal data assistant, handheld device, or laptop computer). The remote device may receive calculated analyte concentrations, alerts, and/or alarms from the transceiver 101 and display them”).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the above-described teachings of Emken, which teaches a wireless implantable device comprising a sensor configured to detect, in real time, activity data from a tissue cluster of an organ, detecting an auto-fluorescence value, and an external transceiver configured to transmit the activity data to the external device, with the invention of Ho in order to sense the concentration of analytes in tissue via in vivo detection (Emken ¶[0012]) and to communicate analyte concentrations with an external device and display the analyte concentrations to a user (Emken ¶[0036]).
Ho does not teach that the activity data comprises a quantity of reactive oxygen species of the organ determined by detecting an auto-fluorescence value from the tissue cluster of the organ from which the quantity of reactive oxygen species of the organ is determined, a transceiver configured to transmit the activity data to the external device, nor that the processing unit is configured to update the stimulation parameters based on the activity data. Additionally, although Emken teaches a sensor that is configured to detect, in real time, activity data from a tissue cluster of an organ, detecting an auto-fluorescence value, and a transceiver configured to transmit activity data to the external device, Emken does not explicitly teach that the activity data comprises a quantity of reactive oxygen species of the organ determined by detecting an auto-fluorescence value from the tissue cluster of the organ from which the quantity of reactive oxygen species of the organ is determined nor that the transceiver is a component of the wireless implantable device.
Schnermann teaches fluorescent compounds and irradiating the sample with a quantity of light having a wavelength in the visible or near-infrared range and a selected intensity, where the quantity of light is sufficient to produce fluorescence and fluorescence indicates the presence of ROS in the sample (¶0011]), and further teaches that the activity data comprises a quantity of reactive oxygen species of the organ determined by detecting an auto-fluorescence value from the tissue cluster of the organ from which the quantity of reactive oxygen species of the organ is determined (¶[0011], where “if reactive oxygen species (ROS) are present in the sample; irradiating the sample with a quantity of light having a wavelength in the visible or near-infrared range and a selected intensity, wherein the quantity of light is sufficient to produce fluorescence if the reduced compound has been oxidized by the ROS … and detecting any fluorescence emitted by the compound according to Formula I, wherein fluorescence indicates the presence of ROS in the sample,” ¶[0145], where “ROS have been implicated in a variety of inflammatory diseases, such as cancer and atherosclerosis. ROS detection can be performed in vitro, ex vivo, or in vivo … ROS present in the sample may oxidize the compound to recreate the fluorophore, which is detected by any suitable method. Fluorescence indicates the presence of ROS in the sample. The intensity of the fluorescence may be correlated to the concentration of ROS in the sample”).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the above-described teachings of Schnermann, which teaches that the activity data comprises a quantity of reactive oxygen species of the organ determined by detecting an auto-fluorescence value from the tissue cluster of the organ from which the quantity of reactive oxygen species of the organ is determined, with the modified invention of Ho since ROS have been implicated in a variety of inflammatory diseases, such as cancer and atherosclerosis (Schnermann ¶[0145]), and ROS detection can aid in the mitigation of disease.
Although Emken teaches a transceiver configured to transmit activity data to the external device, Emken does not explicitly teach that the transceiver is a component of the wireless implantable device. Additionally, none of Ho, Emken, nor Schnermann teach that the processing unit is configured to update the stimulation parameters based on the activity data.
Denison teaches an implantable medical system with a therapy delivery module that comprises a light source that generates light and a controller that controls the output of the light source to target tissue, where a sensing module determines a patient’s therapeutic state based on the sensed bioelectric signals substantially simultaneously with the delivery of light from the light source, wherein the controller is configured to adjust the delivery of light to the target tissue based on the sensed patient therapeutic state (Abstract), and further teaches a wireless implantable device comprising: a transceiver (¶[0101], where “programmer 40 may communicate to implantable stimulator 34 or any other computing device via wireless communication. Programmer 40, for example, may communicate via wireless communication with implantable stimulator 34 using radio frequency (RF) telemetry techniques known in the art,” ¶[0103], where “implantable stimulator 34 includes … telemetry module 56,” ¶[0114], where “telemetry module 56 may include a radio frequency (RF) transceiver to permit bi-directional communication between implantable stimulator 34 and each of clinician programmer 20 and patient programmer 22”), and
wherein the processing unit (¶[0114], where “telemetry module 56 may permit communication with clinician programmer 20 and patient programmer 22 in FIG. 1”) is configured to update the stimulation parameters based on the activity data (¶[0031], where “As non-limiting examples, the optical stimulation may be delivered to target tissue within the brain or spinal cord of a human patient. However, the disclosure is not so limited. Rather, optical stimulation may be delivered to any of a variety of target tissue sites to support any of a variety or therapies,” ¶[0153], where “An optogenetic modulation system such as system 2 of FIG. 1 provides for closed-loop feedback of the optical stimulation being generated by stimulator …simultaneous sensing allows processor 50 or an external programmer, such as clinician programmer 20 or patient programmer 22, to not only record the effect of the performed optical stimulation, but also to provide a feedback loop that allows for adjustments to the treatment parameters of subsequent optical stimulations. ” Examiner takes the position that closed-loop feedback and control is equivalent to updating stimulation parameters based on activity data.).
It would have been obvious to one of ordinary skill in the art at the time of the invention to incorporate the above-described teachings of Denison, which teaches a wireless implantable device comprising: a transceiver and that the processing unit is configured to update the stimulation parameters based on the activity data, into the modified invention of Ho in order to allow for bi-directional communication between an implantable stimulator and the external device (Denison ¶[0114]), to record the effect of the performed optical stimulations, and to provide a feedback loop that allows for adjustments to the treatment parameters of subsequent optical stimulations (Denison ¶[0153]) that triggers initiation or adjustment of optical stimulation to alleviate patient symptoms (Denison ¶[0172]).
Regarding claim 4, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Emken teaches that the detecting of the activity data in real time by the sensor further comprises detecting an additional auto-fluorescence value associated with at least one of a plurality of molecules (¶[0041], where “sensor 100 also includes one or more photodetectors 110 (e.g., photodiodes, phototransistors, photoresistors, or other photosensitive elements) which, in the case of a fluorescence-based sensor, is sensitive to fluorescent light emitted by the indicator molecules 104 such that a signal is generated by the photodetector 110 in response thereto that is indicative of the level of fluorescence of the indicator molecules and, thus, the amount of analyte of interest (e.g., glucose).” Examiner takes the position that since there are multiple photodetectors, where one or more teaches multiple, that sense fluorescent light emitted by indicator molecules, that an additional auto-fluorescence value is detected as there is more than one auto-fluorescence value being sensed.).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the above-described teachings of Emken, which teaches that the detecting of the activity data in real time by the sensor further comprises detecting an additional auto-fluorescence value associated with at least one of a plurality of molecules, with the invention of Ho in order to sense the concentration of analytes in tissue via in vivo detection (Emken ¶[0012]).
Regarding claim 6, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Ho teaches that one of the plurality of light components includes a light emitting diode that is configured to emit a first light (¶[0004], where “the light source comprises a first light emitting device configured to emit light having a first wavelength,” ¶[0117], where “the wireless implantable illumination device 3110 is a thin, flexible device, which comprises mesh of light emitting diode (LEDs)”).
Regarding claim 7, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 6 as described in the rejection above.
Although Ho teaches the first light and that an appropriate wavelength or spectrum of wavelengths is chosen (¶[0063], where “the implantable illumination device 110 to illuminate the target lesion 106 with light 122 having a wavelength or spectrum of wavelengths selected to activate the photosensitizer 108”), Ho does not explicitly teach a wavelength of 488 nanometers.
Denison teaches a wavelength of 488 nanometers (¶[0034], where “light that may be used to provide the optical stimulation of system 2 may include visible light having a wavelength of between about 380 nm and about 750 nm.” Examiner takes the position that the range of Denison of 380 nm to 750 nm encompasses a wavelength of 488 nm.).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the above-described teachings of Denison, which teaches a wavelength of 488 nanometers, with the invention of Ho in order to apply light at a wavelength that has a physiologically measurable effect (Denison ¶[0034]).
Regarding claim 8, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Ho teaches that another one of the plurality of light components includes an additional light emitting diode that is configured to emit a second light (¶[0004], where “the light source comprises … a second light emitting device configured to emit light having a second wavelength different from the first wavelength”).
Regarding claim 9, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 8 as described in the rejection above.
Ho teaches that the second light corresponds to a wavelength of 405 nanometers (¶[0121], where “devices can be customized to emit a suitable light wavelength ... LED meshes that emit either 405 nm … light”).
Regarding claim 10, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Ho teaches that the plurality of light components being coupled to the flexible elastomer includes a first light component embedded in a first portion of the flexible elastomer and at least a second light component embedded in a second portion of the flexible elastomer (Figure 32, LEDs 3240, which are connected in parallel across the circuit and being placed in a first and second portion of the substrate 3210, ¶[0118], where “the implantable illumination device 3110 is formed from on a substrate 3210. The substrate 3210 is formed from a flexible material such as polyimide.” Examiner takes the position that since the device comprises of a first and second light source that is formed on a substrate made of polyamide, where polyamide is a flexible elastomer, that this is equivalent to the light components being embedded in a flexible elastomer.).
Regarding claim 11, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Ho teaches that the flexible elastomer is configured to attach to the tissue cluster of the organ (¶[0092], where “the device was implanted in the abdomen and ROS detection was carried out in the area surrounding the device ... the device was placed 5.1 cm deep, on the liver surface.” Examiner takes the position that since the device is place on the liver surface that it will inherently attach to a tissue cluster of the organ, here the liver.).
Regarding claim 22, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Ho teaches that the stimulator is configured to activate operation of the tissue cluster of the organ (¶[0117], where “FIG. 31 shows an implantable illumination device for treatment of a brain tumor … the wireless implantable illumination device 3110 is a thin, flexible device, which comprises mesh of light emitting diode (LEDs). This allows the wireless implantable illumination device 3110 to be implanted in the narrow confines beneath the skull of the subject. The wireless implantable illumination device 3110 is implanted close to the glioblastoma 3120 and as described above, light emitted from the wireless implantable illumination device 3110 activates a photosensitizer 3130 in the vicinity of the glioblastoma 3120,” ¶[0118], where “FIG. 32 shows the implantable illumination device shown in FIG. 31.” Examiner interprets that by stimulating the brain, an organ, to treat a brain tumor that this activates operation of the tissue cluster of the organ, where activation occurs since treatment of a brain tumor will restore brain function.).
Regarding claim 23, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Ho teaches that the flexible elastomer (¶[0118], where “substrate 3210 is formed from a flexible material such as polyimide.” Examiner takes the position that the flexible material is an elastomer since polyamide is a type of elastomer.) protrudes from a flexible printed circuit board (¶[0118], where “the implantable illumination device 3110 is formed from on a substrate 3210. The substrate 3210 is formed from a flexible material such as polyimide.” Examiner interprets that the flexible substrate is equivalent to a flexible printed circuit board since the substrate houses the electronic components. Furthermore, the flexible elastomer, or polyamide, protrudes from the flexible printed circuit board since they are formed of the same substrate, where the elastomer will protrude since it is not a two-dimensional object.) within which the stimulator and antenna are embedded (¶[0118], where “The substrate 3210 is circular and a receiver antenna 3220 is formed as circular loop of copper on the substrate 3210 around the edge … A plurality of light emitting diodes (LEDs) 3240 are connected in parallel across the direct current (DC) output of the rectifier 3230”).
Denison teaches that the sensor is embedded within the circuit board (¶[0114], where “Alternatively, antenna 57 may be mounted on a circuit board carrying other components of implantable stimulator 34,” ¶[0118], where “FIG. 4 is a block diagram illustrating various components of another example implantable stimulator 34. Like the implantable stimulator 34 shown in FIG. 3, the example of FIG. 4 includes an optical stimulation generator 60, a processor 50, memory 52, a telemetry module 56, and a power source 54 which have the same general configurations as described above for the example of FIG. 3 … stimulator 34 of FIG. 4 also includes sensing circuitry 65 electrically coupled to one or more leads 49 A, 49B (collectively referred to as "leads 49") that each carry one or more sense electrodes.” Examiner interprets that since the components of implantable stimulator 34 may be mounted on a circuit board, that the sensing circuitry, which is a sensor, is also mounted on a circuit board.)
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the above-described teachings of Denison, which teaches that the sensor is embedded within the circuit board, with the modified invention of Ho in order to mount and house the sensor.
Regarding claim 24, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Ho teaches that a distal end of the flexible elastomer (¶[0118], where “FIG. 32 shows the implantable illumination device shown in FIG. 31. As shown in FIG. 32, the implantable illumination device 3110 is formed from on a substrate 3210.” Examiner takes the position that the flexible material is an elastomer since polyamide is a type of elastomer.) is attached to the tissue cluster of the organ (¶[0117], where “FIG. 31 shows an implantable illumination device for treatment of a brain tumor … the wireless implantable illumination device 3110 is a thin, flexible device, which comprises mesh of light emitting diode (LEDs). This allows the wireless implantable illumination device 3110 to be implanted in the narrow confines beneath the skull of the subject.” Examiner interprets that a distal end of the flexible elastomer is attached to the tissue cluster of the organ because the brain is an organ on which the implantable illumination device is implanted, where a distal end of the substrate 3210 that the implantable illumination device 3110 is formed on contacts the brain.).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Emken, Schnermann, and Denison as applied to claim 4 above, and further in view of Croce et al. (hereinafter “Croce”) (Croce, A., Ferrigno, A., Di Pasqua, L., Berardo, C., Piccolini, V., Bertone, V., Bottiroli, G., Vairetti, M. (2016). Autofluorescence discrimination of metabolic fingerprint in nutritional and genetic fatty liver models. Journal of Photochemistry and Photobiology B: Biology, 164, 13-20. https://doi.org/10.1016/j.jphotobiol.2016.09.015.).
Regarding claim 5, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 4 as described in the rejection above.
None of Ho, Emken, Schnermann, nor Denison teaches that the plurality of molecules include proteins, arachidonic acid, and flavins.
Croce teaches the analysis of liver tissue fluorescence (Abstract), and further teaches that the plurality of molecules include proteins, arachidonic acid, and flavins (Page 13, Col. 1, where “Autofluorescence (AF) based real-time diagnostic applications in biomedicine provide many clues to the normal or altered state of cells and tissues” for “monitoring of liver functionality under ischemia and during organ preservation for transplantation,” and “AF investigations have relied primarily on NAD(P)H and flavins as biomarkers of energy metabolism and redox state of cells and tissues … More recently, the attention given to additional EFs, such as proteins … fluorescing fatty acids,” Page 14, Col. 2, where the fluorescing fatty acids include arachidonic acid).
It would have been obvious to one of ordinary skill in the art at the time of the invention to incorporate the above-described teachings of Croce, which teaches that the plurality of molecules include proteins, arachidonic acid, and flavins, into the modified invention of Ho since autofluorescence (AF) based real-time diagnostic applications in biomedicine provide many clues to the normal or altered state of cells and tissues (Croce Page 13, Col. 1) such as oxidative damages due to the hyperproduction of reactive oxygen species (ROS) from the increased oxidation of fatty acids which impairs organ functionality in surgery and transplantation (Croce Page 13, Col. 2).
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Ho in view of Emken, Schnermann, and Denison as applied to claim 1 above, and further in view of Gretz et al. (hereinafter “Gretz”) (U.S. Pub. No. 2011/0230739 A1).
Regarding claim 21, Ho in combination with Emken, Schnermann, and Denison teaches all limitations of claim 1 as described in the rejection above.
Emken teaches that the sensor comprises a photodiode (¶[0008], where “the light may be reflected by the tissue or may cause the tissue to fluoresce and return light at a different wavelength. The reflected and fluoresced light from the tissue may return through the … other transparent part of the sensor and may be received by one or more light detectors (e.g., photodiodes) of the sensor,” ¶[0041], where “sensor 100 also includes one or more photodetectors 110 (e.g., photodiodes, phototransistors, photoresistors, or other photosensitive elements)”).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the above-described teachings of Emken, which teaches that the sensor comprises a photodiode, with the modified invention of Ho in order to sense the concentration of analytes in tissue via in vivo detection (Emken ¶[0012]) and to communicate analyte concentrations with an external device and display the analyte concentrations to a user (Emken ¶[0036]).
Although Emken teaches a photodiode, Emken does not explicitly teach that the photodiode is configured to sense green roGFP fluorescence, and none of Ho, Emken, Schnermann, nor Denison teach sensing green roGFP fluorescence.
Gretz teaches a sensor plaster for the transcutaneous measurement of an organ function (Abstract), and further teaches a sensor configured to sense green roGFP fluorescence (¶[0026], where “the response light can be shifted toward longer wavelengths in comparison with the interrogation light, which is generally the case for example in a fluorescence measurement … The detector and/or the detector in interaction with the at least one response filter can accordingly be designed to detect such response light … the detector and/or the detector in interaction with the at least one response filter can be designed to detect response light having a measurable intensity in the range of between 510 nm and 530 nm, in particular at 520 nm.” Examiner interprets that the sensor is configured to sense green roGFP fluorescence since the emission wavelength for green roGFP fluorescence is between 520 nm as described in ¶[0023] of Applicant’s specification.).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the above-described teachings of Gretz, which teaches a sensor configured to sense green roGFP fluorescence, with the modified invention of Ho in order to measure organ function (Gretz ¶[0001]).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Van Der Mark et al. (WO 2009050667), which teaches “that the intensity of the backscattered light portion received at the proximal end of said light guiding means can be measured … There are various well-known ways to characterize tissue by light, for instance based on elastic backscattering and absorption (measured as a function of wavelength) or based on inelastic backscattering properties, such as e.g. fluorescence … When being illuminated, protoporphyrin IX can produce fluorescence but can also react with oxygen, thus giving rise to very reactive oxygen radicals that can lead to necrosis, which is the basis of the photodynamic therapy. Said photosensitizer can thereby be applied in various well-known ways” (Page 15, ¶ 3 – Page 16, ¶ 1).
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/SEFRA D. MANOS/Examiner, Art Unit 3792
/ALLEN PORTER/Primary Examiner, Art Unit 3796
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