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 Amendment
The amendment filed 10/24/2025 has been entered. Claims 1-22 remain pending in the application.
Claim Objections
Claims 5, 8, and 18 are objected to because of the following informalities:
In claim 5, lines 1-2, “a pancreas of a patient using Low-Intensity Non-Focused Ultrasound (LINFU) at a first setting” should read “the pancreas of the patient using Low-Intensity Non-Focused Ultrasound (LINFU) at the first setting”, because using LINFU at a first setting has been recited in claim 1.
In claim 8, line 1, the “a pancreas of a patient using Low-Intensity Non-Focused Ultrasound (LINFU) at a first setting;” should read “the pancreas of the patient using Low-Intensity Non-Focused Ultrasound (LINFU) at the first setting”, because using LINFU at a first setting has been recited in claim 1.
In claim 18, line 3, “a LINFU device” should read “the LINFU device”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 1-7 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Rutenberg et al (WO 2019183623), hereinafter Rutenberg, in view of Powers (US 20100056924), hereinafter Powers.
Regarding claim 1, Rutenberg teaches a method for producing an organ-sized area of stable microbubble cavitation (“introducing microbubbles the organ or tissue, such as a pancreas… wide area ultrasound energy” [0009]; “insonating the tissue of the subject with an amount of ultrasonic energy effective to elicit stable cavitation of the ultrasound contrast agent so as to thereby elicit exfoliation of cells or tissue fragments from the in a subject and then collecting a cell sample from the tissue in the subject” [00018]) comprising:
insonating an organ of a patient (“a pancreas” [0009]) using Low Intensity Non-Focused Ultrasound (LINFU) at a first setting (“the method includes administering an ultrasound contrast agent that forms microbubbles in a patient’s circulatory system and insonating the subject. After introducing microbubbles the organ or tissue, such as a pancreas, is subjected to wide area ultrasound energy. The ultrasound application of embodiments of the invention may be described as Low Intensity Non-Focused Ultrasound (LINFU). In embodiments of the invention, the ultrasound energy combined with the energy exerted by the microbubbles causes pancreatic cells and, optionally, tissue fragments to disassociate and/or exfoliate.” [0009]; “the ultrasonic energy is unfocused in the pancreas of a subject.” [00056]);
monitoring, via computer, the organ to detect presence of desired stable cavitation microbubble resonance and presence of unwanted inertial cavitation (“the methods further comprise monitoring the subject for implosion of microbubbles or ultrasound contrast agent during at least a portion of the insonating of the subject.” [00053]; “the ultrasound energy is emitted from an transducer array that includes several cavitation detectors for monitoring and localizing cavitation during the procedure.” [00077]. The “stable cavitation” implies microbubble resonance, i.e., stable microbubble oscillations caused by ultrasound while the “implosion” is unstable inertial cavitation).
Rutenberg does not teach that when the presence of stable cavitation microbubble resonance is not detected then automatically adjusting, via computer, insonation parameters so as to increase the level of insonation; and when inertial cavitation is detected then automatically adjusting, via computer, the insonation parameters so as to decrease the level of insonation.
However, in the ultrasonic microbubble cavitation field of endeavor, Powers discloses control and display of ultrasonic microbubble cavitation, which is analogous art. Powers teaches that when the presence of stable cavitation microbubble resonance (“SC”) is not detected (“If no cavitation is detected in the image the pointer will point to zero.” [0031]; Fig. 6) then automatically adjusting (“allowing the user to automatically … control the cavitation mode." [0023]), via computer (18)( Note that the court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art. MPEP 2144.04.III, In re Venner), insonation parameters so as to increase the level of insonation (“Detection of the mode of cavitation is used to automatically or manually control the mode of cavitation by controlling the transmitted acoustic energy of the system.” Abstract. “Another approach is to increase transmit power to a level just below the occurrence of significant or detectable energy in the IC band. Thus, stable cavitation is maintained without the onset of undesired inertial cavitation. This is of considerable benefit in transcranial applications because the skull is highly attenuative and varies from person to person. It is very difficult to predict in advance the transmit power level needed to maintain stable cavitation in the head of a particular patient. The present invention solves this problem by detecting and identifying the type of cavitation then allowing the user to automatically … control the cavitation mode." [0023]); and
when inertial cavitation (“IC”) is detected (“if the power is turned too high and inertial cavitation begins, the pointer will move to the IC indication” [0031]) then automatically adjusting (“allowing the user to automatically … control the cavitation mode." [0023]), via computer (18) (“The user interface is also coupled to the transmit controller 18 to control the generation of ultrasound signals from the transducer arrays 10a and 10b ... The transmit parameters controlled in response to user adjustment include the MI (Mechanical Index) which controls the peak intensity or power of the transmitted waves, which is related to cavitational effects of the ultrasound" [0017]; Fig. 1. Note that the court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art. MPEP 2144.04.III, In re Venner.), the insonation parameters so as to decrease the level of insonation (“allowing the user to automatically … control the cavitation mode." [0023] “FIG. 6 also shows a display indicator 304 which displays the type of cavitation detected. The pointer 306 of the display indicator can point at zero, SC, or IC or between these indications. The instantaneous setting of the pointer 306 is determined by a signal from the cavitation comparator to indicate the predominant type of cavitation detected. If no cavitation is detected in the image the pointer will point to zero. As stable cavitation begins to manifest itself the pointer will move to the SC indication, and if the power is turned too high and inertial cavitation begins, the pointer will move to the IC indication. The pointer can indicate an average or overall cavitation content of the vasculature by summing or integrating the cavitation signals over the points in the image where microbubbles have been detected. The user adjusts the transmit power level to keep the pointer 306 pointing continually at the SC indication.” [0031]).
Therefore, based on Powers’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Rutenberg to have the steps of when the presence of stable cavitation microbubble resonance is not detected then automatically adjusting, via computer, insonation parameters so as to increase the level of insonation; and when inertial cavitation is detected then automatically adjusting, via computer, the insonation parameters so as to decrease the level of insonation, as taught by Powers, in order to generate desired cavitation in the target anatomy thereby reducing or eliminating the organ damage during cavitation.
Regarding claim 2, Rutenberg modified by Powers teaches the method according to claim 1, wherein Rutenberg teaches that the organ is a pancreas and monitoring the pancreas comprises: producing ultrasound images of the pancreas (“the ultrasound imaging is used to assist placement of a transducer which emits the ultrasonic energy over the organ or over the pancreas.” [00090]); and
monitoring for microbubble resonance by detecting the microbubble resonance in the ultrasound images (“The animal was insonated with single frequency ultrasound at a Mechanical Index of 1.3 to 1.4 (e.g. at 2.0Mz) for 10 minutes via a transducer placed on the skin of the animal approximately 3-4 inches directly above the pancreas of the animal. The correct placing of the ultrasound transducer was effected by observing the appearance of opaqueness in the pancreas when the ultrasound was placed correctly” [000136]).
Regarding claim 3, Rutenberg modified by Powers teaches the method according to claim 2.
Rutenberg does not teach that detecting the microbubble resonance in the ultrasound images comprises performing image analysis of the ultrasound images.
However, in the ultrasonic microbubble cavitation field of endeavor, Powers discloses control and display of ultrasonic microbubble cavitation, which is analogous art. Powers teaches that detecting the microbubble resonance in the ultrasound images comprises performing image analysis of the ultrasound images (“summing or integrating the cavitation signals over the points in the image where microbubbles have been detected” [0031]) (“Either the adaptive or manual technique can be used, in conjunction with the flow (Doppler) information if desired, to detect signals coming from microbubbles. When a microbubble has been detected at a spatial location in the image, the "bubble detect" signal triggers the graphics processor 36 in FIG. 5 to place a color in a color overlay of the image 302 which indicates the type of cavitation at each bubble location. The color is determined by a cavitation signal coupled to the graphics processor from the cavitation comparator 70. For instance, if the SC signal or SC/IC ratio indicates the presence of stable cavitation at a location where a bubble is detected, a green color is added to the overlay at that bubble location, as indicated by the single hatching 90 in FIG. 6. But when inertial cavitation is detected by the cavitation comparator, a different color is added to the overlay such as a red color at that bubble location. The red color is indicated by cross-hatching 92 in FIG. 6…The cavitation color overlay is combined with the ultrasound image by the ultrasound image processor 30.” [0029] “FIG. 6 also shows a display indicator 304 which displays the type of cavitation detected. The pointer 306 of the display indicator can point at zero, SC, or IC or between these indications. The instantaneous setting of the pointer 306 is determined by a signal from the cavitation comparator to indicate the predominant type of cavitation detected…As stable cavitation begins to manifest itself the pointer will move to the SC indication…The pointer can indicate an average or overall cavitation content of the vasculature by summing or integrating the cavitation signals over the points in the image where microbubbles have been detected. The user adjusts the transmit power level to keep the pointer 306 pointing continually at the SC indication.” [0031]).
Therefore, based on Powers’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Rutenberg to have the step of detecting the microbubble resonance in the ultrasound images that comprises performing image analysis of the ultrasound images, as taught by Powers, in order to generate desired cavitation in the target anatomy.
Regarding claim 4, Rutenberg modified by Powers teaches the method according to claim 2, wherein Rutenberg teaches that monitoring the pancreas comprises monitoring for inertial cavitation by cavitation detectors (“the ultrasound energy is emitted from an transducer array that includes several cavitation detectors for monitoring and localizing cavitation during the procedure.” [00077]).
Regarding claim 5, Rutenberg modified by Powers teaches the method according to claim 1, wherein Rutenberg teaches that the organ is a pancreas and the insonating comprises insonating the pancreas of the patient (“a pancreas” [0009]) using Low Intensity Non-Focused Ultrasound (LINFU) at the first setting (“the method includes administering an ultrasound contrast agent that forms microbubbles in a patient’s circulatory system and insonating the subject. After introducing microbubbles the organ or tissue, such as a pancreas, is subjected to wide area ultrasound energy. The ultrasound application of embodiments of the invention may be described as Low Intensity Non-Focused Ultrasound (LINFU). In embodiments of the invention, the ultrasound energy combined with the energy exerted by the microbubbles causes pancreatic cells and, optionally, tissue fragments to disassociate and/or exfoliate.” [0009]; “the ultrasonic energy is unfocused in the pancreas of a subject.” [00056]); and; the monitoring comprises monitoring the patient for inertial cavitation (“the methods further comprise monitoring the subject for implosion of microbubbles or ultrasound contrast agent during at least a portion of the insonating of the subject.” [00053]; “the ultrasound energy is emitted from an transducer array that includes several cavitation detectors for monitoring and localizing cavitation during the procedure.” [00077].
Rutenberg does not teach identifying a depth of the inertial cavitation; and
automatically adjusting insonation when the depth of the inertial cavitation is greater than a depth of an anterior surface of the pancreas.
However, in the ultrasonic microbubble cavitation field of endeavor, Powers discloses control and display of ultrasonic microbubble cavitation, which is analogous art. Powers teaches identifying a depth of the inertial cavitation (“Tissues in the body and microbubbles both return both types of signals and the stronger harmonic returns of microbubbles enable microbubbles to be clearly segmented in an image in most applications…The structural and motion signals produced by these processors are coupled to a scan converter 32 and a volume renderer 34, which produce image data of tissue structure, flow, or a combined image of both characteristics. The scan converter will convert echo signals with polar coordinates into image signals of the desired image format such as a sector image in Cartesian coordinates. The volume renderer 34 will convert a 3D data set into a projected 3D image as viewed from a given reference point” [0016]. “When a microbubble has been detected at a spatial location in the image, the "bubble detect" signal triggers the graphics processor 36 in FIG. 5 to place a color in a color overlay of the image 302 which indicates the type of cavitation at each bubble location. The color is determined by a cavitation signal coupled to the graphics processor from the cavitation comparator 70… But when inertial cavitation is detected by the cavitation comparator, a different color is added to the overlay such as a red color at that bubble location. The red color is indicated by cross-hatching 92 in FIG. 6…The cavitation color overlay is combined with the ultrasound image by the ultrasound image processor 30.” [0029]; “In the example of FIG. 6 it is seen … that inertial cavitation (cross-hatching 92) is occurring in the center of the major vessel 80.” [0030]. A depth of the inertial cavitation is being identified at least with respect to the “given reference point”); and
automatically adjusting insonation when the depth of the inertial cavitation is greater than a depth of an anterior surface of the organ (80) (“Detection of the mode of cavitation is used to automatically … control the mode of cavitation by controlling the transmitted acoustic energy of the system.” Abstract; “detecting and identifying the type of cavitation then allowing the user to automatically … control the cavitation mode" [0023]; “inertial cavitation (cross-hatching 92) is occurring in the center of the major vessel 80. A user trying to maintain stable cavitation will then turn down the transmit power until the red color 92 is replaced with the green color 90, indicating the presence of only stable cavitation in the vasculature.” [0030]).
Therefore, based on Powers’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Rutenberg to have the steps of identifying a depth of the inertial cavitation; and
automatically adjusting insonation when the depth of the inertial cavitation is greater than a depth of an anterior surface of the organ, as taught by Powers, in order to generate desired cavitation in the target anatomy. In the invention of Rutenberg and Powers, the organ is the pancreas.
Regarding claim 6, Rutenberg modified by Powers teaches the method according to claim 5, wherein Rutenberg teaches controlling insonation to avoid causing tissue damage (“In order to increase the yield of cells of interest, e.g. abnormal cells in a fluid sample from the body, the subject invention utilizes an application of ultrasound energy, preferably at a level that is safe for diagnostic purposes (e.g. Mechanical Index (“MI”) of 1.9 or lower).” [000118]).
Regarding claim 7, Rutenberg modified by Powers teaches the method according to claim 5, wherein Rutenberg teaches that the insonating the pancreas of the patient comprises insonating a first portion of the pancreas (“insonating a pancreas of the subject with an amount of ultrasonic energy from a multi -frequency array effective to achieve an asymmetric ultrasound wave at a predetermined point in the pancreas and elicit exfoliation of cells into a duct of a pancreas in the subject.” [00015]; “the method is effective to elicit exfoliation of an epithelial tissue fragment of the pancreas.” [00049]); and
Rutenberg does not teach the automatically adjusting insonation comprises steering the insonation to a second, different, portion of the pancreas.
However, in the ultrasonic microbubble cavitation field of endeavor, Powers discloses control and display of ultrasonic microbubble cavitation, which is analogous art. Powers teaches steering the insonation to a second, different, portion of the organ (“The transmit parameters controlled in response to user adjustment include …steering of the transmitted beams for image positioning and/or positioning (steering) of a therapy beam as discussed below.” [0017]. “If examination finds a blood vessel occluded by a blood clot, a therapeutic beam 110 or 112 is transmitted and steered at the clot to break it up either with the ultrasonic energy alone, but preferably in combination with microbubbles” [0018]).
Therefore, based on Powers’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Rutenberg to have the step of steering the insonation to a second, different, portion of the organ, as taught by Powers, in order to generate desired cavitation in the target anatomy. In the invention of Rutenberg and Powers, the organ is the pancreas.
Regarding claim 22, Rutenberg modified by Powers teaches the method according to claim 2, wherein Rutenberg teaches that the organ-sized area of stable microbubble cavitation comprises substantially the size of the pancreas (“introducing microbubbles the organ or tissue, such as a pancreas… wide area ultrasound energy” [0009]; “the ultrasonic energy is unfocused in the pancreas of a subject.” [00056]; “the ultrasound imaging is used to assist placement of a transducer which emits the ultrasonic energy over the organ or over the pancreas.” [00090]).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Rutenberg and Powers as applied to claim 1, and further in view of Rousso et al (US 20200188696), hereinafter Rousso.
Regarding claim 8, Rutenberg modified by Powers teaches the method according to claim 1, wherein Rutenberg teaches that the organ is a pancreas of the patient and insonating a pancreas of the patient (“a pancreas” [0009]) using Low Intensity Non-Focused Ultrasound (LINFU) at a first setting (“the method includes administering an ultrasound contrast agent that forms microbubbles in a patient’s circulatory system and insonating the subject. After introducing microbubbles the organ or tissue, such as a pancreas, is subjected to wide area ultrasound energy. The ultrasound application of embodiments of the invention may be described as Low Intensity Non-Focused Ultrasound (LINFU). In embodiments of the invention, the ultrasound energy combined with the energy exerted by the microbubbles causes pancreatic cells and, optionally, tissue fragments to disassociate and/or exfoliate.” [0009]; “the ultrasonic energy is unfocused in the pancreas of a subject.” [00056]); and; the monitoring comprises monitoring the patient for inertial cavitation (“the methods further comprise monitoring the subject for implosion of microbubbles or ultrasound contrast agent during at least a portion of the insonating of the subject.” [00053]; “the ultrasound energy is emitted from an transducer array that includes several cavitation detectors for monitoring and localizing cavitation during the procedure.” [00077].
Rutenberg as modified by Powers does not teach determining temperature produced by the insonating;
automatically adjusting insonation when the temperature exceeds a threshold temperature.
However, in the medical treatments field of endeavor, Rousso discloses apparatus and method for treating kidneys, which is analogous art. Rousso teaches determining temperature produced by the insonating; automatically adjusting insonation when the temperature exceeds a threshold temperature (“the system comprises one or more temperature sensors (e.g., by analyzing temperature sensitive imaging sequences, such as MRI or ultrasound imaging sequences) or receive information indicative of temperature, that evaluates the temperature changes and threshold near the one or more transducers, and/or at different tissue locations. In some embodiments, the system adjusts the signal amplitude, main frequencies, and/or duration and/or duty cycles and/or repetition rates, and/or burst duration, to avoid heating accumulation beyond a certain predefined level, for example by keeping the energy delivery parameters at less than 0.9 or less than 0.5 or less than 0.3 or less than 0.1 or less than 0.05 (or intermediate values) of the values that could be identified as potentially causing undesired heating. In some embodiments, the sensors are implanted sensors in the body of the subject.” [0225]).
Therefore, based on Rousso’ teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the combined invention of Rutenberg and Powers to have the steps of determining temperature produced by the insonating; automatically adjusting insonation when the temperature exceeds a threshold temperature, as taught by Rousso, in order to improve safety of the ultrasonic treatments by reducing tissue damage from heating.
Claims 9-10, 12-13, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Powers (US 20100056924), hereinafter Powers, in view of Rutenberg et al (WO 2019183623), hereinafter Rutenberg
Regarding claim 9, Powers teaches an ultrasound device (Figs. 1 and 5) comprising:
an ultrasound probe (60) comprising an ultrasound transducer (10) (“FIG. 5 is a detailed block diagram of one implementation of the concepts of the present invention in the ultrasound system of FIG. 1. An ultrasound probe 60 has a transducer array 10 coupled by T/R switch 16 to a transmit beamformer 20a which controls the transmission of therapeutic beams by the transducer array 10 and to a receive beamformer 20b which beamforms echo signals received from the transducer array elements 10.” [0026]);
a cavitation detector (62);
an electronics unit (12a-b, 14, 16, 18, 20a) for adjusting insonation of the ultrasound probe (“Signals are routed to and from the microbeamformers by a multiplexer 14 by time-interleaving signals. The multiplexer is coupled to a transmit/receive (T/R) switch 16 which switches between transmission and reception and protects the main beamformer 20 from high energy transmit signals. The transmission of ultrasonic beams from the transducer arrays 10a and 10b under control of the microbeamformers 12a and 12b is directed by the transmit controller 18 coupled to the T/R switch, which received input from the user's operation of the user interface or control panel 38.” [0013]; Fig. 5); and
a processor (70) for analyzing signals from the cavitation detector and controlling the insonation using the electronics unit (“Received echoes are analyzed by frequency and a significant subharmonic response is identified as stable cavitation. The analysis may compare the subharmonic response with a harmonic response to identify stable cavitation… In an automatic mode the transmitted energy is adjusted automatically to acquire or maintain the desired cavitation.” [0005]. “The signal content of the SC and IC bands is then analyzed by a cavitation comparator 70 which may analyze the SC signal content alone for its energy content or in comparison with a threshold level, or may analyze the SC signal content in comparison with the IC signal content as described previously. The result of the analysis will indicate the presence of stable cavitation, inertial cavitation, or both or neither.” [0026]; Fig. 5), wherein the processor is configured to automatically adjust insonation parameters so as to increase a level of insonation (“allowing the user to automatically … control the cavitation mode." [0023] Note that the court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art. MPEP 2144.04.III, In re Venner) when the presence of stable cavitation microbubble resonance (“SC”) is not detected (“If no cavitation is detected in the image the pointer will point to zero.” [0031]; Fig. 6) (“Detection of the mode of cavitation is used to automatically … control the mode of cavitation by controlling the transmitted acoustic energy of the system.” Abstract. “Another approach is to increase transmit power to a level just below the occurrence of significant or detectable energy in the IC band. Thus, stable cavitation is maintained without the onset of undesired inertial cavitation. This is of considerable benefit in transcranial applications because the skull is highly attenuative and varies from person to person. It is very difficult to predict in advance the transmit power level needed to maintain stable cavitation in the head of a particular patient. The present invention solves this problem by detecting and identifying the type of cavitation then allowing the user to automatically … control the cavitation mode." [0023]); and
to automatically adjust the insonation parameters so as to decrease the level of insonation when inertial cavitation (“IC”) is detected (“if the power is turned too high and inertial cavitation begins, the pointer will move to the IC indication” [0031]) (“The user interface is also coupled to the transmit controller 18 to control the generation of ultrasound signals from the transducer arrays 10a and 10b ... The transmit parameters controlled in response to user adjustment include the MI (Mechanical Index) which controls the peak intensity or power of the transmitted waves, which is related to cavitational effects of the ultrasound" [0017]; Fig. 1; “allowing the user to automatically … control the cavitation mode." [0023] “FIG. 6 also shows a display indicator 304 which displays the type of cavitation detected. The pointer 306 of the display indicator can point at zero, SC, or IC or between these indications. The instantaneous setting of the pointer 306 is determined by a signal from the cavitation comparator to indicate the predominant type of cavitation detected. If no cavitation is detected in the image the pointer will point to zero. As stable cavitation begins to manifest itself the pointer will move to the SC indication, and if the power is turned too high and inertial cavitation begins, the pointer will move to the IC indication. The pointer can indicate an average or overall cavitation content of the vasculature by summing or integrating the cavitation signals over the points in the image where microbubbles have been detected. The user adjusts the transmit power level to keep the pointer 306 pointing continually at the SC indication.” [0031], Fig. 6. Note that the court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art. MPEP 2144.04.III, In re Venner).
Powers does not teach that the ultrasound device is a Low Intensity Non-Focused Ultrasound (LINFU) device.
However, in the ultrasonic microbubble cavitation field of endeavor, Rutenberg discloses a method to induce exfoliation of cells and/or tissue fragments for enhanced cytopathologic cell collection, which is analogous art. Rutenberg teaches a Low Intensity Non-Focused Ultrasound (LINFU) device (“the method includes administering an ultrasound contrast agent that forms microbubbles in a patient’s circulatory system and insonating the subject. After introducing microbubbles the organ or tissue, such as a pancreas, is subjected to wide area ultrasound energy. The ultrasound application of embodiments of the invention may be described as Low Intensity Non-Focused Ultrasound (LINFU). In embodiments of the invention, the ultrasound energy combined with the energy exerted by the microbubbles causes pancreatic cells and, optionally, tissue fragments to disassociate and/or exfoliate.” [0009]; “the ultrasonic energy is unfocused in the pancreas of a subject.” [00056]).
Therefore, based on Rutenberg’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Powers to employ the ultrasound device that is a Low Intensity Non-Focused Ultrasound (LINFU) device, as taught by Rutenberg, in order to improve generation of desired cavitation in the target anatomy without causing a tissue damage.
Regarding claim 10, Powers modified by Rutenberg teaches the device according to claim 9.
Powers does not teach that the ultrasound transducer is configured to provide an approximately uniform field of ultrasonic insonation over an area a size of a human organ, wherein the human organ is a pancreas.
However, in the ultrasonic microbubble cavitation field of endeavor, Rutenberg discloses a method to induce exfoliation of cells and/or tissue fragments for enhanced cytopathologic cell collection, which is analogous art. Rutenberg teaches that the ultrasound transducer is configured to provide an approximately uniform field of ultrasonic insonation over an area a size of a human organ, wherein the human organ is a pancreas (“administering an ultrasound contrast agent that forms microbubbles in a patient’s circulatory system and insonating the subject. After introducing microbubbles the organ or tissue, such as a pancreas, is subjected to wide area ultrasound energy. The ultrasound application of embodiments of the invention may be described as Low Intensity Non-Focused Ultrasound (LINFU). In embodiments of the invention, the ultrasound energy combined with the energy exerted by the microbubbles causes pancreatic cells and, optionally, tissue fragments to disassociate and/or exfoliate.” [0009]; “the ultrasonic energy is unfocused in the pancreas of a subject.” [00056]; “a transducer which emits the ultrasonic energy over the organ or over the pancreas.” [00090]).
Therefore, based on Rutenberg’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Powers to employ the ultrasound transducer that is configured to provide an approximately uniform field of ultrasonic insonation over an area a size of a human organ, wherein the human organ is a pancreas, as taught by Rutenberg, in order to improve generation of desired cavitation in the target anatomy without causing a tissue damage.
Regarding claim 12, Powers modified by Rutenberg teaches the device according to claim 9, wherein Powers teaches that the processor is configured to determine a depth of cavitation detected by the cavitation detector cavitation (“Tissues in the body and microbubbles both return both types of signals and the stronger harmonic returns of microbubbles enable microbubbles to be clearly segmented in an image in most applications…The structural and motion signals produced by these processors are coupled to a scan converter 32 and a volume renderer 34, which produce image data of tissue structure, flow, or a combined image of both characteristics… The volume renderer 34 will convert a 3D data set into a projected 3D image as viewed from a given reference point” [0016]. “When a microbubble has been detected at a spatial location in the image, the "bubble detect" signal triggers the graphics processor 36 in FIG. 5 to place a color in a color overlay of the image 302 which indicates the type of cavitation at each bubble location. The color is determined by a cavitation signal coupled to the graphics processor from the cavitation comparator 70… But when inertial cavitation is detected by the cavitation comparator, a different color is added to the overlay such as a red color at that bubble location. The red color is indicated by cross-hatching 92 in FIG. 6…The cavitation color overlay is combined with the ultrasound image by the ultrasound image processor 30.” [0029]; “In the example of FIG. 6 it is seen … that inertial cavitation (cross-hatching 92) is occurring in the center of the major vessel 80.” [0030]. The processor is configured to determine a depth of cavitation at least with respect to the “given reference point”).
Regarding claim 13, Powers modified by Rutenberg teaches the device according to claim 12, wherein Powers teaches that the processor is configured to determine a three dimensional location of cavitation (“a spatial location” [0029]) detected by the cavitation detector (“the arrays shown are two dimensional arrays of transducer elements capable of scanning in three dimensions for 3D imaging and treatment” [0013]; “The volume renderer 34 will convert a 3D data set into a projected 3D image as viewed from a given reference point" [0016]. “When a microbubble has been detected at a spatial location in the image, the "bubble detect" signal triggers the graphics processor 36 in FIG. 5 to place a color in a color overlay of the image 302 which indicates the type of cavitation at each bubble location…The cavitation color overlay is combined with the ultrasound image by the ultrasound image processor 30.” [0029]; “In the example of FIG. 6 it is seen … that inertial cavitation (cross-hatching 92) is occurring in the center of the major vessel 80.” [0030]).
Regarding claim 18, Powers modified by Rutenberg teaches the LINFU device according to claim 9.
Powers teaches a system for producing an organ-sized area of stable microbubble cavitation (“An ultrasonic diagnostic imaging system is used to insonify a subject infused with a microbubble contrast agent. At low energy levels stable cavitation occurs as the bubbles oscillate radially without breaking up." Abstract) comprising:
a device (Figs. 1 and 5) (“FIG. 5 is a detailed block diagram of one implementation of the concepts of the present invention in the ultrasound system of FIG. 1. An ultrasound probe 60 has a transducer array 10 coupled by T/R switch 16 to a transmit beamformer 20a which controls the transmission of therapeutic beams by the transducer array 10 and to a receive beamformer 20b which beamforms echo signals received from the transducer array elements 10.” [0026]); and
a user interface (38) configured for entering parameters related to producing stable microbubble resonance while avoiding inertial cavitation (“In a manual implementation the user will control the transmit power from the transmit power control of the user interface 38. As the user increases power from a low power setting with microbubbles present, stable cavitation will begin to occur, producing subharmonic energy in the SC passband which is detected by the cavitation comparator, either alone or in combination with higher frequency energy of the IC passband. When stable cavitation is identified by the cavitation comparator 70 a control signal is coupled to a user alert 72 which issues an audible or visual alert to the user. The audible alert can comprise a tone of a given frequency or amplitude from a speaker 42 when stable cavitation is detected, and can change to or be mixed with a tone of a different frequency or sound when inertial cavitation is detected. The user will thus adjust the power level until the stable cavitation tone is continuously heard without interruption by the inertial cavitation tone.” [0028]; Fig. 5).
In the combined invention of Powers and Rutenberg, the device is according to claim 9.
Regarding claim 19, Powers modified by Rutenberg teaches the device according to claim 18, wherein Powers teaches that the user interface is configured for entering physical parameters related to a subject (“As the user increases power from a low power setting with microbubbles present, stable cavitation will begin to occur, producing subharmonic energy in the SC passband which is detected by the cavitation comparator, either alone or in combination with higher frequency energy of the IC passband…The user will thus adjust the power level until the stable cavitation tone is continuously heard without interruption by the inertial cavitation tone.” [0028]. “In the example of FIG. 6 it is seen … that inertial cavitation (cross-hatching 92) is occurring in the center of the major vessel 80.” [0030]).
Powers does not teach a subject planned for exfoliation.
However, in the ultrasonic microbubble cavitation field of endeavor, Rutenberg discloses a method to induce exfoliation of cells and/or tissue fragments for enhanced cytopathologic cell collection, which is analogous art. Rutenberg teaches a subject planned for exfoliation (“the method includes administering an ultrasound contrast agent that forms microbubbles in a patient’s circulatory system and insonating the subject. After introducing microbubbles the organ or tissue, such as a pancreas, is subjected to wide area ultrasound energy. The ultrasound application of embodiments of the invention may be described as Low Intensity Non-Focused Ultrasound (LINFU). In embodiments of the invention, the ultrasound energy combined with the energy exerted by the microbubbles causes pancreatic cells and, optionally, tissue fragments to … exfoliate.” [0009]).
Therefore, based on Rutenberg’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the invention of Powers to employ the user interface that is configured for entering physical parameters related to a subject planned for exfoliation, as taught by Rutenberg, in order to improve diagnostic procedures by reducing or eliminating unnecessary tissue damage.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Powers and Rutenberg as applied to claim 9, and further in view of Ogasawara et al (WO 2013042773), hereinafter Ogasawara.
Regarding claim 11, Powers modified by Rutenberg teaches the device according to claim 9.
Powers modified by Rutenberg does not teach that the ultrasound probe is shaped to fit between a patient's ribs, below the patient's sternum.
However, in the ultrasonic-wave diagnostics field of endeavor, Ogasawara discloses ultrasonic diagnosis device, which is analogous art. Ogasawara teaches that the ultrasound probe (301) is shaped to fit between a patient's ribs, below the patient's sternum (“As shown in FIGS. 14 and 15, the ultrasonic probe 301 according to the second modification includes an exterior case in which concave portions 304 a and 304 b that are substantially linear depressions are formed on a contact surface 304… Such an ultrasonic probe 301 is easy to be fixed to the subject P because the concave portions 304a and 304b have a shape that can be easily fitted between the ribs. Specifically, since the ultrasonic probe 301 has an exterior case 303 having recesses 304a and 304b formed at both ends of the acoustic lens 105, the recesses 304a and 304b are the ribs of the subject P in the example…For this reason, the ultrasonic probe 301 is easily fixed to the subject P, and as a result, it is possible to steadily image a fixed part (for example, the heart) in the subject P.”; p. 12, para. 2-3).
Therefore, based on Ogasawara’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined invention of Powers and Rutenberg to employ the ultrasound probe that is shaped to fit between a patient's ribs, below the patient's sternum, as taught by Ogasawara, in order to improve imaging of subject’s internal organs.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Powers and Rutenberg as applied to claim 13, and further in view of Slayton et al (US 9533175), hereinafter Slayton.
Regarding claim 14, Powers modified by Rutenberg teaches the device according to claim 13.
Powers modified by Rutenberg does not teach a component for removing heat from the ultrasound probe.
However, in the ultrasonic-wave treatments field of endeavor, Slayton discloses energy-based fat reduction, which is analogous art. Slayton teaches a component (306) for removing heat from the ultrasound probe (“Cooling/coupling control systems 306 may be provided to remove waste heat from exemplary probe 104, provide a controlled temperature at the superficial tissue interface and deeper into tissue, and/or provide acoustic coupling from transducer probe 104 to ROI 210. Such cooling/coupling control systems 306 can also be configured to operate in both open-loop and/or closed-loop feedback arrangements with various coupling and feedback components”; col. 10, l. 15-22; fig. 3A).
Therefore, based on Slayton’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined invention of Powers and Rutenberg to employ a component for removing heat from the ultrasound probe, as taught by Slayton, in order to reduce tissue damage from heat generated by the probe by providing a controlled tissue temperature.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Powers and Rutenberg as applied to claim 9, and further in view of Partsch et al (WO 2013082587), hereinafter Partsch.
Regarding claim 15, Powers modified by Rutenberg teaches the device according to claim 9.
Powers modified by Rutenberg does not teach a belt for attaching to a subject's body.
However, in the ultrasonic-wave treatments field of endeavor, Partsch discloses a method for modulating the enteric nervous system to treat a disorder, which is analogous art. Partsch teaches a belt for attaching to a subject's body (“The neuromodulation probe may comprise … an ultrasound transducer... The neuromodulation probe may be configured to rest against the subject's torso. In some variations the system includes a … belt, or other securing structure configured to secure the neuromodulation probe against the subject's torso during a treatment period (and in some cases between treatment periods).” [00044]).
Therefore, based on Partsch’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined invention of Powers and Rutenberg to employ a belt for attaching to a subject's body, as taught by Partsch, in order to secure the probe against the subject's torso during a treatment period.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Powers, Rutenberg, and Partsch as applied to claim 15, and further in view of Rousso et al (US 20200188696), hereinafter Rousso.
Regarding claim 16, Powers modified by Rutenberg and Partsch teaches the device according to claim 15.
Rutenberg as modified by Powers does not teach a temperature sensor for measuring temperature at a subject's body.
However, in the medical treatments field of endeavor, Rousso discloses apparatus and method for treating kidneys, which is analogous art. Rousso teaches a temperature sensor for measuring temperature at a subject's body (“the system comprises one or more temperature sensors (e.g., by analyzing temperature sensitive imaging sequences, such as MRI or ultrasound imaging sequences) or receive information indicative of temperature, that evaluates the temperature changes and threshold near the one or more transducers, and/or at different tissue locations. In some embodiments, the system adjusts the signal amplitude, main frequencies, and/or duration and/or duty cycles and/or repetition rates, and/or burst duration, to avoid heating accumulation beyond a certain predefined level, for example by keeping the energy delivery parameters at less than 0.9 or less than 0.5 or less than 0.3 or less than 0.1 or less than 0.05 (or intermediate values) of the values that could be identified as potentially causing undesired heating. In some embodiments, the sensors are implanted sensors in the body of the subject.” [0225]).
Therefore, based on Rousso’ teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the combined invention of Powers, Rutenberg, and Partsch to have a temperature sensor for measuring temperature at a subject's body, as taught by Rousso, in order to improve safety of the ultrasonic treatments by reducing tissue damage from heating.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Powers, Rutenberg, Partsch, and Rousso as applied to claim 16, and further in view of Slayton et al (US 9533175), hereinafter Slayton.
Regarding claim 17, Powers modified by Rutenberg, Partsch, and Rousso teaches the device according to claim 16.
Powers modified by Rutenberg does not teach a temperature sensor for measuring temperature at the ultrasound probe.
However, in the ultrasonic-wave treatments field of endeavor, Slayton discloses energy-based fat reduction, which is analogous art. Slayton teaches a temperature sensor for measuring temperature at the ultrasound probe (“Transducer probe 202 may also be configured for control of other environment parameters, e.g., the temperature at the acoustic coupling interface can be controlled.” Col. 7, l. 67 – col. 8, l. 3. Claim 3. “The system of claim 1, further comprising a monitoring system, … wherein the ultrasound probe further comprises a temperature monitoring sensor.” Col. 26).
Therefore, based on Slayton’s teachings, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the combined invention of Powers, Rutenberg, Partsch, and Rousso to employ a temperature sensor for measuring temperature at the ultrasound probe, as taught by Slayton, in order to reduce tissue damage from heat generated by the probe by providing a controlled tissue temperature.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Powers and Rutenberg as applied to claim 18, and further in view of Miao et al (US20210370037), hereinafter Miao.
Regarding claim 20, Powe