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 .
Claim Objections
Claims 1-5, 7, 9-11, and 18 are objected to because of the following informalities:
In claim 1, line 6, “the patient's skull” should read – a skull of the human patient or --the human patient's skull--.
In claim 1, line 10; claim 4, line 1; and claims 10-11, line 2, “the target tissue” should read –the target ICH--.
In claim 1, the “determining” para., line 2; and claim 7, lines 2-3; “the detected ultrasound pulses” should read –the detected test ultrasound pulses--.
In claim 2, the “histotripsy pulses” should read –the histotripsy pulses--.
In claim 3, line 4, “the test ultrasound pulses” should read –the second test ultrasound pulses--.
In claim 3, line 7, “the detected ultrasound pulses” should read –the detected second test ultrasound pulses--.
In claim 3, in the “determining" para., line 1, the “ultrasound pulses” should read –electronically steered ultrasound pulses-- for consistency with the electronically steered ultrasound pulses in the “determining" para., line 3.
In claim 5, lines 5, 8; claim 7, line 5, and claim 9, line 2, “the therapy transducer” should read – the therapy transducer array--.
In claim 7, lines 4-5, “a plurality of transducer elements” should read –the plurality of transducer elements--.
In claims 7 and 18, lines 11 and 10, respectively, “to the to the midpoint” should read –to the midpoint--.
In claim 12, line 4 and the "ultrasound therapy transducer" para., line 2, “a skull … a skullcap” should read, for example, –a skullcap … the skullcap--, for consistency.
In claim 12, the "electronic controller" para., line 2, “the piezoelectric sensors” should read –the one or more piezoelectric sensors--.
In claim 12, the "electronic controller" para., line 4, “ultrasound pulses” should read –the ultrasound pulses--.
In claim 16, lines 4 and 6, “the therapy transducer” should read –the ultrasound therapy transducer --.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 5 and 7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 5 recites “adjusting the transmission of ultrasound pulses from the plurality of transducer elements with the aberration correction algorithm based on the detected ultrasound pulses further comprises”. There is insufficient antecedent basis for this limitation because the “adjusting” and the aberration correction algorithm have not been recited in claim 1. Additionally, the antecedent basis is unclear for the “detected ultrasound pulses.” It is unclear whether or not this is a reference to the test ultrasound pulses in claim 1. For examination purposes, Examiner of record takes this to be “automatically correcting for the aberration effect further comprises”.
Claim 7 recites “adjusting the transmission of ultrasound pulses from the plurality of transducer elements with the aberration correction algorithm based on the detected ultrasound pulses further comprises”. There is insufficient antecedent basis for this limitation because the “adjusting” and the aberration correction algorithm have not been recited in claims 1 and 6. Additionally, the antecedent basis is unclear for the “detected ultrasound pulses.” It is unclear whether or not this is a reference to the test ultrasound pulses in claim 1. For examination purposes, Examiner of record takes this to be “automatically correcting for the aberration effect further comprises”.
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 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Hynynen (WO 98007373), hereinafter Hynynen, in view of Nita (US 20110319927), hereinafter Nita, Ahn et al (US 20130144194), hereinafter, Ahn, and Hansmann et al. (US 20060173387), hereinafter Hansmann.
Regarding claim 1, Hynynen teaches a method of transmitting ultrasound energy into a brain of a human patient (14) (“In step 30, the array is excited, e.g., by control and driving elements 18-22, to focus ultrasound in the patient's head. As noted throughout, because the invention provides correction for phased distortion induced by the skull, that ultrasound can be supplied directly through the skull without the need for removal of a piece thereof."; p. 10, l. 26-30; “the invention provides methods and apparatus for noninvasive diagnosis and treatment of the brain using cavitational mechanism and pulsed ultrasound. It permits adequate power transmission through the human skull can be induced to cause tissue damage while keeping the exposures in the overlying tissues below the cavitation threshold.”; p. 21, l. 27 – p. 22, l. 2; Fig. 10), comprising the steps of:
imaging the brain (“using MRI” p.20, l.10-17) to identify a target (“the target volume” p.20, l.10-17) (“Our results demonstrate that low frequency beams can be focused through the skull, though, the focus may be shifted from its geometric location. Therefore, it can be helpful to detect the focal spot location in the brain prior to the therapy exposure, e.g., using magnetic resonance imaging…low power test exposures can be delivered through the skull while using MRI to detect the location of the focal spot. Based on the imaging information the location can be corrected to overlap the target volume prior to the therapeutic exposure.”; p.20, l.10-17);
attaching a stereotactic frame (“a plastic holder”; p. 14, l. 14-16; “the scanning frame”; p. 15, l. 1-4) to the patient's skull (seen in Fig. 10);
coupling a semi-spherical therapy transducer array (12) (“The array 12 can constitute a single transducer, e.g., a spherically curved piezoelectric bowl of the type described below, though preferably, array 12 comprises a plurality of transducers arranged in a one-, two- or three-dimensional configuration.”; p. 7, l. 10-15; “a spherically curved 10 cm diameter piezoelectric ceramic (PZT4) bowl mounted in a plastic holder using silicon rubber. “; p. 14, l. 14-16) and an acoustic coupler to the stereotactic frame (“The tank was filled with degassed deionized water.”; p. 15, l. 1-4; Fig. 10);
positioning a focus (“the focal spot.” p.20, l.10-17) of a plurality of transducer elements of the therapy transducer array within the target tissue (“low power test exposures can be delivered through the skull while using MRI to detect the location of the focal spot.” p.20, l.10-17);
transmitting test ultrasound pulses from each of the plurality of transducer elements (“low power test exposures can be delivered” p.20, l.10-17) towards a natural focus (“the geometric focus”; p. 18, 22-32; “its geometric location” p.20, l.10-17) of the therapy transducer array (“Our results demonstrate that low frequency beams can be focused through the skull, though, the focus may be shifted from its geometric location…low power test exposures can be delivered through the skull while using MRI to detect the location of the focal spot. Based on the imaging information the location can be corrected to overlap the target volume prior to the therapeutic exposure.”; p.20, l.10-17);
detecting the test ultrasound pulses with one or more piezoelectric sensors (“implanting small hydrophones in the patient's brain”; p. 9, l. 24-27. Note that small hydrophones are small piezoelectric transducers) (“the hydrophone was connected to the scanning frame, and positioned at the focus of the ultrasound field.” p. 15, l. 1-4); and
determining a set of time delays (“recording the time difference” p. 18, l. 15-20) to add to ultrasound pulses from the plurality of transducer elements based on the detected ultrasound pulses (“calculating the phase correction required for each array element… by sending a short ultrasound pulse from each or selected elements of the of the phased array and then listening for the echo back from the inner surfaces of the skull or other structures in the brain.”; p. 21, l. 7-15) to automatically correct for an aberration effect caused by the ultrasound pulses passing through the patient's skull ("To measure the phase distortion caused by the skull, a hydrophone was placed in the geometric focus of the array under test. The skull was placed between the array and hydrophone and each transducer element was powered separately in sequence while recording the time difference between the reference signal and the acoustic wave at the focus. This was done with both of the arrays. The phase changes required to correct all of the waves to arrive at the same phase at the focus are plotted in Figure 6.”; p. 18, l. 15-20; “when phase correction was introduced, the focal spot was returned into its original shape (Figure 9c) with the half-width of the focus of about 1 mm.”; p. 19, l. 1-4. “In step 30, the array is excited, e.g., by control and driving elements 18-22, to focus ultrasound in the patient's head. As noted throughout, because the invention provides correction for phased distortion induced by the skull, that ultrasound can be supplied directly through the skull without the need for removal of a piece thereof."; p. 10, l. 26-30; Fig. 10);
delivering histotripsy pulses with the set of time delays to liquefy the target (“cavitation requires negative pressure amplitudes that are large enough to form gas bubbles in the tissue. The pressure wave causes the bubbles to expand and then collapse. The collapse of the bubbles causes high temperatures and pressures that can cause direct mechanical damage to the tissue. Cavitation can offer more therapeutic options than thermal exposures of brain”; p. 13, l. 10-16. “Cavitation requires high pressure amplitudes but only short exposure durations, therefore cavitational effects can be induced without significant temperature elevation. For CNS tissues, sonications with durations of only 1 ms are adequate for bubble formation… Thermal exposures can be further reduced using multiple pulses that can be repeated at a low frequency (for example 0.1 Hz) thus, eliminating a temperature build up.”; p. 13, l. 28-p. 14, l.10. “The results also show that adequate ultrasound transmission can be induced through human skull to induce cavitation in vivo.”; p. 19, l. 19-22).
Hynynen does not teach that target is intracerebral hemorrhage (ICH);
determining 3D coordinates of the ICH and a margin of the ICH;
placing a drainage catheter within the ICH;
one or more piezoelectric sensors positioned on or in the drainage catheter;
evacuating the liquefied ICH from the patient with the drainage catheter.
However, in the treatments of intracranial hematoma field of endeavor, Nita discloses methods and apparatus for removing blood clots from intracranial aneurysms, which is analogous art. Nita teaches intracerebral hemorrhage (ICH) (“An intracranial hematoma occurs when a blood vessel ruptures within the brain ... Removing or reducing hematoma in the brain is crucial to the patient's recovery. Catheter-based evacuation is a novel surgical approach for the treatment of brain hematoma. Such a minimally invasive treatment of intracranial hematoma may help prevent complications and promote illness recovery, reduce morbidity and improve cure rate, and reduce medical costs. Removal of hematoma is performed using extraventicular drains (EVD) or drainage catheters. These drainage catheters or introducers placed inside hematoma not only provide a path for the brain to keep it decompressed, but also provide a channel to remove or reduce hematoma outside the patient's head.” [0011]);
placing a drainage catheter within the ICH (“These drainage catheters … placed inside hematoma” [0011]);
evacuating the liquefied ICH from the patient with the drainage catheter (“Catheter-based evacuation is a novel surgical approach for the treatment of brain hematoma. Such a minimally invasive treatment of intracranial hematoma may help prevent complications and promote illness recovery, reduce morbidity and improve cure rate, and reduce medical costs. Removal of hematoma is performed using … drainage catheters. These drainage catheters … placed inside hematoma not only provide a path for the brain to keep it decompressed, but also provide a channel to remove or reduce hematoma outside the patient's head.” [0011]. “Dissolved blood clots maybe removed outside the head via … any other suitable catheter.” [0033]).
Therefore, based on Nita’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 Hynynen to have a target that is intracerebral hemorrhage (ICH); place a drainage catheter within the ICH; and evacuate the liquefied ICH from the patient with the drainage catheter, as taught by Nita, in order to help prevent complications and promote illness recovery, reduce morbidity and improve cure rate, and reduce medical costs.
Hynynen modified by Nita does not teach determining 3D coordinates of the ICH and a margin of the ICH.
However, in the ultrasonic treatments field of endeavor, Ahn discloses a method and apparatus for making ultrasonic irradiation plan based on anatomical features, which is analogous art. Ahn teaches determining 3D coordinates of the ICH (“the virtual 3D target object model” [0055]) and a margin of the ICH (“the normal tissue in the target object,” [0043]) (“Examples of the data received from the user may include information about a movement pattern of a lesion, an obstacle, or a normal tissue, information indicating the lesion, the obstacle, or the normal tissue in the target object,” [0043]. “When 2D medical image data is received in the receiving unit 210, the target object model generating unit 222 generates 3D medical image data by accumulating a plurality of the 2D medical image data received by the receiving unit 210 from the medical imaging instrument 100, designates the lesion, obstacle, and normal tissue recognized by the image analyzing unit 221 in a 3D virtual target object represented by the 3D medical image data, and generates the virtual 3D target object model of the designated lesion, obstacle, or normal tissue” [0055]; “check the virtual 3D target object model having the predicted shape to determine whether the lesion is removed or the normal tissue is protected, and determine a location of the transducer where ultrasonic irradiation is allowed based on a result of the checking whether the lesion is removed or the normal tissue is protected.” [0060]).
Therefore, based on Ahn’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 further modified the combined invention of Hynynen and Nita to employ the steps of determining 3D coordinates of the ICH and a margin of the ICH, as taught by Ahn, in order reduce complications and promote illness recovery, reduce morbidity and improve cure rate, and reduce medical costs.
Hynynen modified by Nita and Ahn does not teach one or more piezoelectric sensors positioned on or in the drainage catheter.
However, in the ultrasonic treatments field of endeavor, Hansmann discloses externally enhanced ultrasonic therapy, which is analogous art. Hansmann teaches one or more piezoelectric sensors (124) positioned on or in the catheter (“An ultrasound radiating member coupled to an ultrasound catheter, or a guidewire used with a catheter, is capable of receiving ultrasonic energy as well as generating ultrasonic energy.” [0030], “receive ultrasonic energy generated from an internal ultrasound radiating member.” [0036]; “the information provided from an ultrasound radiating member operating as a microphone is used to automatically adjust certain characteristics of an ultrasonic energy field.” [0039] “the ultrasound radiating member 124 comprises a transducer formed of a piezoelectric ceramic oscillator” [0050]).
Therefore, based on Hansmann’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 further modified the combined invention of Hynynen, Nita, and Ahn to have one or more piezoelectric sensors positioned on or in the catheter, as taught by Hansmann, in order to facilitate intracranial ultrasonic treatments by automatically adjusting certain characteristics of an ultrasonic energy field. In the combined invention of Hynynen, Nita, Ahn, and Hansmann, the catheter is the drainage catheter.
Regarding claim 2, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 1, wherein Hynynen teaches delivering the histotripsy pulses in a focal grid pattern without treating the margin (“spaced grid of simple hemispherical sources”; p. 26, right col.; “the desired field pattern… a set of different focal spots for a given array”; p. 43, left col.).
Regarding claim 3, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 1, wherein Hynynen teaches transmitting second test ultrasound pulses from each of the plurality of transducer elements (“low power test exposures can be delivered” p.20, l.10-17) towards one or more discrete electronically steered focal locations (“the location of the focal spot” p.20, l.10-17) (“The phase shift factors, α,, a^ α.sub.3, etc. serve two purposes. The first is to steer the composite ultrasound beam generated by transducer array 12 so that it is focused on a desired region within the patient's brain. The component of each phase shift factor associated with steering is computed in the manner known in the art for steering phased arrays.”; p. 8, l. 25 – p. 9, l. 10);
detecting the test ultrasound pulses with the one or more piezoelectric sensors (“the hydrophone was connected to the scanning frame, and positioned at the focus of the ultrasound field.” p. 15, l. 1-4); and
determining additional sets of time delays (“recording the time difference” p. 18, l. 15-20) to add to ultrasound pulses from the plurality of transducer elements based on the detected ultrasound pulses to automatically correct for an aberration effect (“These phase shift factors α,, α.sub.2, α.sub.3, etc., can be … generated by a controller 20 …and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10; “calculating the phase correction required for each array element… by sending a short ultrasound pulse from each or selected elements of the of the phased array and then listening for the echo back from the inner surfaces of the skull or other structures in the brain.”; p. 21, l. 7-15) caused by the electronically steered ultrasound pulses passing through the patient's skull at each of the discrete electronically steered focal locations (“The first is to steer the composite ultrasound beam generated by transducer array 12 so that it is focused on a desired region within the patient's brain. The component of each phase shift factor associated with steering is computed in the manner known in the art for steering phased arrays…the two components that make up the phase shift factor for each channel of the driving system 18 are summed in order to determine the composite phase shift factor for the respective channel.”; p. 8, l. 25 – p. 9, l. 10; “when phase correction was introduced, the focal spot was returned into its original shape (Figure 9c) with the half-width of the focus of about 1 mm.”; p. 19, l. 1-4. “In step 30, the array is excited, e.g., by control and driving elements 18-22, to focus ultrasound in the patient's head. As noted throughout, because the invention provides correction for phased distortion induced by the skull, that ultrasound can be supplied directly through the skull without the need for removal of a piece thereof."; p. 10, l. 26-30; Fig. 10).
Hynynen modified by Nita and Ahn does not teach the one or more piezoelectric sensors positioned on or in the drainage catheter.
However, in the ultrasonic treatments field of endeavor, Hansmann discloses externally enhanced ultrasonic therapy, which is analogous art. Hansmann teaches the one or more piezoelectric sensors (124) positioned on or in the catheter (“An ultrasound radiating member coupled to an ultrasound catheter, or a guidewire used with a catheter, is capable of receiving ultrasonic energy as well as generating ultrasonic energy.” [0030], “receive ultrasonic energy generated from an internal ultrasound radiating member.” [0036]; “the information provided from an ultrasound radiating member operating as a microphone is used to automatically adjust certain characteristics of an ultrasonic energy field.” [0039] “the ultrasound radiating member 124 comprises a transducer formed of a piezoelectric ceramic oscillator” [0050]).
Therefore, based on Hansmann’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 further modified the combined invention of Hynynen, Nita, and Ahn to have the one or more piezoelectric sensors positioned on or in the catheter, as taught by Hansmann, in order to facilitate intracranial ultrasonic treatments by automatically adjusting certain characteristics of an ultrasonic energy field. In the combined invention of Hynynen, Nita, Ahn, and Hansmann, the catheter is the drainage catheter.
Regarding claim 4, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 1, wherein Hynynen teaches forming a bubble cloud on the target tissue with the histotripsy pulses (Cavitation requires high pressure amplitudes but only short exposure durations, therefore cavitational effects can be induced without significant temperature elevation. For CNS tissues, sonications with durations of only 1 ms are adequate for bubble formation.” p. 13, l. 28-p. 14, l.10. “The results also show that adequate ultrasound transmission can be induced through human skull to induce cavitation in vivo.”; p. 19, l. 19-22).
Regarding claim 5, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 1, wherein Hynynen teaches that adjusting the transmission of ultrasound pulses from the plurality of transducer elements with the aberration correction algorithm based on the detected ultrasound pulses further comprises:
determining a propagation time for the ultrasound pulses to travel from each of the plurality of transducer elements of the therapy transducer to the one or more piezoelectric sensors (“To measure the phase distortion caused by the skull, a hydrophone was placed in the geometric focus of the array under test. The skull was placed between the array and hydrophone and each transducer element was powered separately in sequence while recording the time difference between the reference signal and the acoustic wave at the focus.”; p. 18, l. 15-20);
calculating a time delay of the propagation time between each of the plurality of transducer elements and a reference element of the therapy transducer (“the time difference between the reference signal and the acoustic wave at the focus.” p. 18, l. 15-20); and
adjusting the transmission of ultrasound pulses from the plurality of transducer elements based on the calculated time delays (“The phase changes required to correct all of the waves to arrive at the same phase at the focus are plotted in Figure 6.”; p. 18, l. 15-20).
Regarding claim 6, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 1, wherein Hynynen teaches that the one or more piezoelectric sensors comprises first and second piezoelectric sensors (“The ultrasound pressure wave distributions were measured using needle hydrophones (spot diameter 0.5 and 1 mm)”; p. 14, l. 24-25).
Regarding claim 7, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 6, wherein Hynynen teaches determining a propagation time (“recording the time difference” p. 18, l. 15-20) for the ultrasound pulses to travel from each of a plurality of transducer elements of the therapy transducer to the first and second piezoelectric sensors (“To measure the phase distortion caused by the skull, a hydrophone was placed in the geometric focus of the array under test. The skull was placed between the array and hydrophone and each transducer element was powered separately in sequence while recording the time difference between the reference signal and the acoustic wave at the focus.”; p. 18, l. 15-20);
calculating a distance between the first and second piezoelectric sensors using projections of the first and second piezoelectric sensors onto a ray from each of the plurality of transducer elements to a midpoint of the first and second piezoelectric sensors (“generated by a controller 20…digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. The controller is capable to perform trigonometry calculations to calculate a distance as claimed);
calculating a travel direction and a time of travel of the ultrasound pulses from each of the plurality of transducer elements to the to the midpoint of the first and second piezoelectric sensors (“generated by a controller 20…digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. The controller is capable to perform trigonometry calculations to calculate a travel direction and a time of travel as claimed);
calculating a stand-off distance between the focus and the midpoint for each of the plurality of transducer elements (“generated by a controller 20…digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. The controller is capable to perform trigonometry calculations to calculate a stand-off distance as claimed); and
calculating a time delay of each of the plurality of transducer elements based on the distance between the first and second piezoelectric sensors, the midpoint, and the stand-off distance (“These phase shift factors α,, α.sub.2, α.sub.3, etc., can be … generated by a controller 20. That controller 20 can be a general purpose, or special purpose, digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. “The phase changes required to correct all of the waves to arrive at the same phase at the focus are plotted in Figure 6.”; p. 18, l. 15-20. The controller is capable to perform trigonometry calculations to calculate a time delay as claimed).
Regarding claim 8, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 1, wherein Hynynen teaches placing the one or more piezoelectric sensors within or adjacent to the focus (“the hydrophone was connected to the scanning frame, and positioned at the focus of the ultrasound field.” p. 15, l. 1-4).
Regarding claim 9, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 1.
Hynynen modified by Nita and Ahn does not teach advancing the drainage catheter through a hole of the therapy transducer.
However, in the ultrasonic treatments field of endeavor, Hansmann discloses externally enhanced ultrasonic therapy, which is analogous art. Hansmann teaches the placing step further comprises advancing the catheter (110) through a hole of the therapy transducer (“In the example embodiment illustrated in FIGS. 5A and 5B, the ultrasound radiating member 124 is configured as a hollow cylinder. As such, the inner core 110 extends through the hollow core of the ultrasound radiating member 124.” [0047]).
Therefore, based on Hansmann’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 further modified the combined invention of Hynynen, Nita, and Ahn to have the step of advancing the drainage catheter through a hole of the therapy transducer, as taught by Hansmann, in order to facilitate intracranial ultrasonic treatments by automatically adjusting certain characteristics of an ultrasonic energy field. In the combined invention of Hynynen, Nita, Ahn, and Hansmann, the catheter is the drainage catheter.
Regarding claim 10, Hynynen modified by Nita, Ahn, and Hansmann teaches the method according to claim 3, wherein Hynynen teaches electronically steering the focus to fully liquefy the target tissue (“The first is to steer the composite ultrasound beam generated by transducer array 12 so that it is focused on a desired region within the patient's brain. The component of each phase shift factor associated with steering is computed in the manner known in the art for steering phased arrays…the two components that make up the phase shift factor for each channel of the driving system 18 are summed in order to determine the composite phase shift factor for the respective channel.”; p. 8, l. 25 – p. 9, l. 10).
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Hynynen, Nita, Ahn, and Hansmann as applied to claim 3, and further in view of Darlington et al (US 20100241005), hereinafter, Darlington.
Regarding claim 11, Hynynen modified by Nita, Ahn, and Hansmann teaches the system according to claim 3.
Hynynen modified by Nita, Lo, and Hansmann does not teach mechanically steering the focus to fully liquefy the target tissue.
However, in the ultrasonic treatments field of endeavor, Darlington discloses office-based system for treating uterine fibroids or other tissues with hifu, which is analogous art. Darlington teaches mechanically steering the focus to fully liquefy the target tissue (“a mechanical … steering apparatus directs the focal zone of a HIFU beam around the perimeter of the elemental treatment volume until the tissue encompassed by the perimeter is ablated.” [0008]).
Therefore, based on Darlington’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 further modified the combined invention of Hynynen, Nita, Ahn, and Hansmann to employ the step of mechanically steering the focus to fully liquefy the target tissue as taught by Darlington, in order to facilitate adjustments of the focal zone of an ultrasound beam.
Claims 12-13 and 15-19 are rejected under 35 U.S.C. 103 as being unpatentable over Hynynen (WO 98007373), hereinafter Hynynen, in view of Crum et al (US 20070004984), hereinafter Crum, and Hansmann et al. (US 20060173387), hereinafter Hansmann.
Regarding claim 12, Hynynen teaches an ultrasound system (10) configured to treat a target tissue in a brain of a human patient (14) (“the invention provides methods and apparatus for noninvasive diagnosis and treatment of the brain using cavitational mechanism and pulsed ultrasound. It permits adequate power transmission through the human skull can be induced to cause tissue damage while keeping the exposures in the overlying tissues below the cavitation threshold.”; p. 21, l. 27 – p. 22, l. 2), comprising:
a pulse generator (22) and an amplifier (“Each channel of that system 18 includes an amplifier”) (“The radio frequency generator 22 can be of any commercially available type... The generator is operated in a conventional way so as to generate an excitation signal, which is amplified and phase- shifted by the individual channels of driving system 18, in order to induce the corresponding transducers of array 12 to radiate ultrasound (e.g., in the range 0.01 MHz to 10 MHz).” Fig. 10);
a stereotactic frame (“a plastic holder”; p. 14, l. 14-16; “the scanning frame”; p. 15, l. 1-4) configured to be attached to a skull of the patient (“a spherically curved 10 cm diameter piezoelectric ceramic (PZT4) bowl mounted in a plastic holder using silicon rubber. “; p. 14, l. 14-16; Fig. 10);
an acoustic coupler (“The tank was filled with degassed deionized water.”; p. 15, l. 1-4; Fig. 10);
an ultrasound therapy transducer (12) operatively coupled to the pulse generator and having a plurality of transducer elements configured to transmit ultrasound pulses through a skullcap of the human patient (“array 12 comprises a plurality of transducers arranged in a one-, two- or three-dimensional configuration.”; p. 7, l. 10-15; Fig. 10) towards a focal point (“the focal spot.” p.20, l.10-17) within the target tissue in the brain (“low power test exposures can be delivered through the skull while using MRI to detect the location of the focal spot.” p.20, l.10-17) to generate cavitation (“Cavitation requires high pressure amplitudes but only short exposure durations, therefore cavitational effects can be induced without significant temperature elevation. For CNS tissues, sonications with durations of only 1 ms are adequate for bubble formation… Thermal exposures can be further reduced using multiple pulses that can be repeated at a low frequency (for example 0.1 Hz) thus, eliminating a temperature build up.”; p. 13, l. 28-p. 14, l.10. “The results also show that adequate ultrasound transmission can be induced through human skull to induce cavitation in vivo.”; p. 19, l. 19-22),
the ultrasound therapy transducer being configured to couple to the stereotactic frame such that the acoustic coupler provides acoustic coupling between the plurality of transducer elements and the patient (“a spherically curved 10 cm diameter piezoelectric ceramic (PZT4) bowl mounted in a plastic holder using silicon rubber. “; p. 14, l. 14-16. “The tank was filled with degassed deionized water.”; p. 15, l. 1-4; Fig. 10);
one or more piezoelectric sensors, adapted to be placed within the brain near the focal point to measure the ultrasound pulses (“implanting small hydrophones in the patient's brain”; p. 9, l. 24-27. “the hydrophone was connected to the scanning frame, and positioned at the focus of the ultrasound field.” p. 15, l. 1-4. Note that small hydrophones are small piezoelectric transducers);
an electronic controller (20) coupled to the pulse generator, the ultrasound therapy transducer, and the piezoelectric sensors of the drainage catheter, the electronic controller being configured to control transmission of the ultrasound pulses and adjust the transmission of ultrasound pulses from each of the plurality of transducer elements (“These phase shift factors α,, α.sub.2, α.sub.3, etc., can be … generated by a controller 20. That controller 20 can be a general purpose, or special purpose, digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10) by executing an aberration correction algorithm based on the ultrasound pulses detected ("To measure the phase distortion caused by the skull, a hydrophone was placed in the geometric focus of the array under test. The skull was placed between the array and hydrophone and each transducer element was powered separately in sequence while recording the time difference between the reference signal and the acoustic wave at the focus. This was done with both of the arrays. The phase changes required to correct all of the waves to arrive at the same phase at the focus are plotted in Figure 6.”; p. 18, l. 15-20) to automatically correct for an aberration effect caused by the ultrasound pulses passing through the skullcap of the human patient (“when phase correction was introduced, the focal spot was returned into its original shape (Figure 9c) with the half-width of the focus of about 1 mm.”; p. 19, l. 1-4. “In step 30, the array is excited, e.g., by control and driving elements 18-22, to focus ultrasound in the patient's head. As noted throughout, because the invention provides correction for phased distortion induced by the skull, that ultrasound can be supplied directly through the skull without the need for removal of a piece thereof."; p. 10, l. 26-30; Fig. 10).
Hynynen does not teach an acoustic coupler configured to be attached to the stereotactic frame;
a drainage catheter comprising one or more piezoelectric sensors, the drainage catheter adapted to be placed within the brain near the focal point to measure the ultrasound pulses; the ultrasound pulses detected by the drainage catheter.
However, in the surgical methods and devices field of endeavor, Crum discloses a method and apparatus for preparing organs and tissues for laparoscopic surgery, which is analogous art. Crum teaches an acoustic coupler (111) configured to be attached to the stereotactic frame (“FIG. 1B schematically illustrates apparatus 105, which includes an ultrasound transducer device 107 (configured to deliver therapeutic ultrasound) supported by a top arm 109, which is brought into contact with liver 101 by an acoustic coupler 111 (used to couple acoustic energy to the liver tissue). Coupler 111 comprises an acoustic-transmissive medium inside a flexible membrane. The membrane is highly elastic to enable it to conform to anatomical structures," [0046]. The membrane coupler can be configured to be attached to the stereotactic frame).
Therefore, based on Crum’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 Hynynen to employ an acoustic coupler configured to be attached to the stereotactic frame, as taught by Crum, in order to facilitate ultrasound wave transmission towards the target tissue to deliver therapeutic ultrasound.
Hynynen modified by Crum does not teach a drainage catheter comprising one or more piezoelectric sensors, the drainage catheter adapted to be placed within the brain near the focal point to measure the ultrasound pulses; the ultrasound pulses detected by the drainage catheter.
However, in the ultrasonic treatments field of endeavor, Hansmann discloses externally enhanced ultrasonic therapy, which is analogous art. Hansmann teaches a drainage catheter (102) comprising one or more piezoelectric sensors (124), the drainage catheter adapted to be placed within the brain near the focal point to measure the ultrasound pulses (“information detected by a microphone include field intensity, field position, field orientation, ultrasound frequency, pulse width and pulse shape.” [0039]); the ultrasound pulses detected by the drainage catheter (“the ultrasound catheter includes one or more ultrasound radiating members that are used as microphones” [0034]; “the information provided from an ultrasound radiating member operating as a microphone is used to automatically adjust certain characteristics of an ultrasonic energy field.” [0039]; “For example, FIGS. 5A and 5B illustrate an exemplary embodiment of an ultrasound catheter that is particularly well suited for use within small vessels of the distal anatomy, such as the remote, small diameter blood vessels located in the brain. The ultrasound catheter generally comprises a multi-component tubular body 102” [0042]; “the ultrasound radiating member 124 comprises a transducer formed of a piezoelectric ceramic oscillator” [0050]).
Therefore, based on Hansmann’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 further modified the combined invention of Hynynen and Crum to have a drainage catheter comprising one or more piezoelectric sensors, the drainage catheter adapted to be placed within the brain near the focal point to measure the ultrasound pulses; and the ultrasound pulses detected by the drainage catheter, as taught by Hansmann, in order to facilitate intracranial ultrasonic treatments by automatically adjusting certain characteristics of an ultrasonic energy field.
Regarding claim 13, Hynynen modified by Crum and Hansmann teaches the system according to claim 12, wherein Hynynen teaches that the ultrasound therapy transducer is configured to transmit histotripsy therapy pulses to generate cavitation to liquefy the target tissue within the brain of the human patient (“cavitation requires negative pressure amplitudes that are large enough to form gas bubbles in the tissue. The pressure wave causes the bubbles to expand and then collapse. The collapse of the bubbles causes high temperatures and pressures that can cause direct mechanical damage to the tissue. Cavitation can offer more therapeutic options than thermal exposures of brain”; p. 13, l. 10-16. “Cavitation requires high pressure amplitudes but only short exposure durations, therefore cavitational effects can be induced without significant temperature elevation. For CNS tissues, sonications with durations of only 1 ms are adequate for bubble formation… Thermal exposures can be further reduced using multiple pulses that can be repeated at a low frequency (for example 0.1 Hz) thus, eliminating a temperature build up.”; p. 13, l. 28-p. 14, l.10. “The results also show that adequate ultrasound transmission can be induced through human skull to induce cavitation in vivo.”; p. 19, l. 19-22).
Regarding claim 15, Hynynen modified by Crum and Hansmann teaches the system according to claim 12, wherein Hynynen teaches that the one or more piezoelectric sensors comprises exactly one piezoelectric sensor (“the hydrophone was connected to the scanning frame, and positioned at the focus of the ultrasound field.” p. 15, l. 1-4).
Regarding claim 16, Hynynen modified by Crum and Hansmann teaches the system according to claim 12, wherein Hynynen teaches that adjusting the transmission of ultrasound pulses from the plurality of transducer elements with the aberration correction algorithm based on the detected ultrasound pulses further comprises:
determining a propagation time for the ultrasound pulses to travel from each of the plurality of transducer elements of the therapy transducer to the one or more piezoelectric sensors (“To measure the phase distortion caused by the skull, a hydrophone was placed in the geometric focus of the array under test. The skull was placed between the array and hydrophone and each transducer element was powered separately in sequence while recording the time difference between the reference signal and the acoustic wave at the focus.”; p. 18, l. 15-20);
calculating a time delay of the propagation time between each of the plurality of transducer elements and a reference element of the therapy transducer (“the time difference between the reference signal and the acoustic wave at the focus.” p. 18, l. 15-20); and
adjusting the transmission of ultrasound pulses from the plurality of transducer elements based on the calculated time delays (“The phase changes required to correct all of the waves to arrive at the same phase at the focus are plotted in Figure 6.”; p. 18, l. 15-20).
Regarding claim 17, Hynynen modified by Crum and Hansmann teaches the system according to claim 12, wherein Hynynen teaches that the one or more piezoelectric sensors comprises first and second piezoelectric sensors (“The ultrasound pressure wave distributions were measured using needle hydrophones (spot diameter 0.5 and 1 mm)”; p. 14, l. 24-25).
Regarding claim 18, Hynynen modified by Crum and Hansmann teaches the system according to claim 17, wherein Hynynen teaches determining a propagation time (“recording the time difference” p. 18, l. 15-20) for the ultrasound pulses to travel from each of a plurality of transducer elements of the therapy transducer to the first and second piezoelectric sensors (“To measure the phase distortion caused by the skull, a hydrophone was placed in the geometric focus of the array under test. The skull was placed between the array and hydrophone and each transducer element was powered separately in sequence while recording the time difference between the reference signal and the acoustic wave at the focus.”; p. 18, l. 15-20);
calculating a distance between the first and second piezoelectric sensors using projections of the first and second piezoelectric sensors onto a ray from each of the plurality of transducer elements to a midpoint of the first and second piezoelectric sensors (“generated by a controller 20…digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. The controller is capable to perform trigonometry calculations to calculate a distance as claimed);
calculating a travel direction and a time of travel of the ultrasound pulses from each of the plurality of transducer elements to the to the midpoint of the first and second piezoelectric sensors (“generated by a controller 20…digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. The controller is capable to perform trigonometry calculations to calculate a travel direction and a time of travel as claimed);
calculating a stand-off distance between the focus and the midpoint for each of the plurality of transducer elements (“generated by a controller 20…digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. The controller is capable to perform trigonometry calculations to calculate a stand-off distance as claimed); and
calculating a time delay of each of the plurality of transducer elements based on the distance between the first and second piezoelectric sensors, the midpoint, and the stand-off distance (“These phase shift factors α,, α.sub.2, α.sub.3, etc., can be … generated by a controller 20. That controller 20 can be a general purpose, or special purpose, digital data processor programmed in a conventional manner in order to generate and apply phase shift factors in accord with the teachings hereof.”; p. 8, l. 17-23; Fig. 10. “The phase changes required to correct all of the waves to arrive at the same phase at the focus are plotted in Figure 6.”; p. 18, l. 15-20. The controller is capable to perform trigonometry calculations to calculate a time delay as claimed).
Regarding claim 19, Hynynen modified by Crum and Hansmann teaches the system according to claim 12.
Hynynen modified by Crum does not teach that the therapy transducer comprises a hole through which the drainage catheter is configured to be advanced into the brain of the human patient.
However, in the ultrasonic treatments field of endeavor, Hansmann discloses externally enhanced ultrasonic therapy, which is analogous art. Hansmann teaches that the therapy transducer (124) comprises a hole through which the drainage catheter (110) is configured to be advanced into the brain of the human patient (“In the example embodiment illustrated in FIGS. 5A and 5B, the ultrasound radiating member 124 is configured as a hollow cylinder. As such, the inner core 110 extends through the hollow core of the ultrasound radiating member 124.” [0047]).
Therefore, based on Hansmann’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 further modified the combined invention of Hynynen and Crum to have the therapy transducer that comprises a hole through which the drainage catheter is configured to be advanced into the brain of the human patient, as taught by Hansmann, in order to facilitate intracranial ultrasonic treatments by automatically adjusting certain characteristics of an ultrasonic energy field.
Conclusion
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/ALEXEI BYKHOVSKI/
Primary Examiner, Art Unit 3798