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
This office action is in response to the communications filed on 11/20/2025, concerning Application No. 18/478,342. The amendments to the claims filed on 11/20/2025 are acknowledged. Presently, claims 1-14 remain pending.
Terminal Disclaimer
The terminal disclaimer filed on 11/20/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 11,813,485 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Information Disclosure Statement
The information disclosure statement filed 11/20/2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Examiner notes that copies of the four DE foreign references were not provided alongside the IDS.
The remaining information disclosure statements (IDS) were submitted on 12/31/2025, 02/04/2026, and 03/11/2026, and these submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, these information disclosure statements are being considered by the examiner.
Claim Objections
Claims 1 and 12-14 are objected to because of the following informalities:
Claim 1, lines 10-11, the limitation “based at least in part on the image, a location of the target tumor, or a tissue type of the target tumor” should be changed to “based at least in part on the image of the at least one target tumor, a location of the at least one target tumor, or a tissue type of the at least one target tumor”;
Claim 4, lines 1-2, the limitation “wherein the treatment volume of the at least one target tumor” should be changed to “wherein the optimal treatment volume of the at least one target tumor”;
Claim 5, lines 1-2, the limitation “wherein the treatment volume of the at least one target tumor” should be changed to “wherein the optimal treatment volume of the at least one target tumor”;
Claim 12, lines 1-2, the limitation “wherein the treatment location comprises” should be changed to “wherein the location of the at least one target tumor comprises”;
Claim 13, lines 1-2, the limitation “wherein the treatment location comprises” should be changed to “wherein the location of the at least one target tumor comprises”; and
Claim 14, lines 1-2, the limitation “wherein the treatment location comprises” should be changed to “wherein the location of the at least one target tumor comprises”.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chevillet et al. (US 2017/0071515 A1, of record, hereinafter Chevillet).
Regarding claim 1, Chevillet discloses a histotripsy therapy system (system 10) (see, e.g., Para. [0046], “the system 10 can deliver a pulsing protocol to provide boiling histotripsy that mechanically fractionates the tissue. During boiling histotripsy, the ultrasound source 400 propagates millisecond-long bursts of non-linear HIFU waves toward the focal region 485 in the tissue 112, and the accumulation of the harmonic frequencies produces shock fronts proximate to the focal region 485. This results in rapid heating of tissue and boiling bubbles at the focal region 485 that liquefy and otherwise mechanically damages the tissue 112”), comprising:
a medical imaging modality (second transducer 430) configured to produce an image of at least one target tumor (see, e.g., Para. [0038], “the system 10 further comprises a second transducer 430 for obtaining an ultrasound image of the tissue mass or suspected tissue mass. The second transducer 430 (when present) may comprise, for example, a diagnostic ultrasound transducer. Although the first ultrasound source 400 and second transducer 430 are shown in FIG. 1 within a single transducer housing (ultrasound wand), one of skill in the art will recognize that the second transducer 430 may also be housed in a separate transducer housing from the first ultrasound source 400 in other embodiments”, and Para. [0056], “the ultrasound source 400 may additionally include a second transducer head 430 for obtaining an image of the tissue mass or suspected tissue mass for monitoring application of the amplified ultrasound energy waveform to the tissue mass or suspected tissue mass. In other embodiments, the second transducer head 430 is housed in a second, separate transducer”);
a histotripsy therapy transducer array (first ultrasound source 400) (see, e.g., Para. [0038], “The system 10 also includes an ultrasound source 400 configured for delivering the high-intensity ultrasound waveform to the target tissue mass or suspected tissue mass of the patient”, and Para. [0056], “The ultrasound source 400 is operatively coupled with one or more components of the system 10 and is configured to administer (e.g., apply, deliver, etc.) the amplified ultrasound energy waveform to a tissue mass or a suspected tissue mass. In some embodiments, such as that shown in FIG. 2, the ultrasound source 400 includes a transducer head 420 including one or more transducer elements 425 and configured to focus the amplified ultrasound energy waveform within a tissue mass or within a suspected tissue mass of a subject”);
a robotic positioning system (positioning device 110) coupled to the histotripsy therapy transducer array (400), the robotic positioning system (110) being configured to place a focus (focus 485) of the histotripsy therapy transducer array (400) within the at least one target tumor (volume of tissue 112) (see, e.g., Para. [0044], “the system 10 can further include a positioning device 110 coupled to the ultrasound source 400 to aid in positioning the focus 485 of the ultrasound source 400 at a desired target site in the tissue. For example, the positioning device 110 can include a three-axis computer-controlled positioning system. The positioning device 110 can also manipulate the ultrasound source 400 to move the focus 485 to different regions in the tissue to mechanically damage larger portions of the tissue 112”, and Para. [0045], “In operation, the ultrasound source 400 is positioned proximate to a volume of tissue 112 (e.g., an organ), and the focus 485 of the ultrasound source 400 is aligned with a target site within the tissue 112 using the positioning device 110”); and
an electronic controller (controller 300) (see, e.g., Para. [0039] and [0041-0043]) configured to derive a treatment plan that includes an optimal treatment volume of the at least one target tumor to be treated that will increase a cell response of releasing tumor antigens based at least in part on the image, a location of the target tumor, or a tissue type of the target tumor (see, e.g., Para. [0028], “Systems and methods configured in accordance with embodiments of the present technology are expected to provide effective minimally invasive (e.g., non-invasive) diagnosis and/or treatment of tissue masses, and facilitate better informed, potentially personalized treatment related decisions while reducing risks commonly associated with conventional methods such as needle biopsy” (emphasis added), and Para. [0037], “The ultrasound source 400 can be an ultrasound transducer that emits high levels of ultrasound energy toward a focus 485. The focus 485 can be a point, plane, region, or volume at which the intensity of the ultrasound energy emitted by the ultrasound source 400 is the highest. For example, the ultrasound source 400 generally has a focal depth equal to the diameter of the ultrasound transducer. The function generator 100 and the amplifier 200 can drive the ultrasound source 400 to radiate HIFU waves that induce boiling bubbles or cavitation proximate to the focus 485 to mechanically disrupt (e.g., reversibly disrupt or damage) the tissue mass or suspected tissue mass” (emphasis added), and Para. [0057], “the transducer head 420 has a generally concave shape, providing an array of transducer elements 425 in a generally concave pattern. The resulting amplified ultrasound energy waveform 480 provided by the ultrasound source 400 includes a focal point 485 located a predetermined focal distance D from the ultrasound source 400. The focal distance D may be selected to correspond to the location (e.g., depth) of a tissue mass or suspected tissue mass T, such that the focal point 485 is located within the tissue mass or suspected tissue mass T of a patient P”, where the focus/focal point 485 corresponds to an optimal volume and location of the target tumor that receives treatment, and where the focus/focal point 485 is selected such that “the intensity of the ultrasound energy emitted by the ultrasound source 400 is the highest”, as stated in Para. [0037], and therefore a cell response resulting from the treatment of the highest intensity of the ultrasound energy being emitted would be increased compared to a lower intensity of emitted ultrasound energy, and Para. [0070], “The ability of ultrasound to stimulate the release of cancer-specific protein biomarkers into the circulation was recently reported, however, physical and biological mechanisms behind it are unclear. In addition, the protein biomarker in that study (carcinoembryonic antigen, CEA) is expressed on the cell surface, thus providing no proof of principal for releasing biomarker molecules from within the cell. Here, the release of a recently established class of intracellular nucleic acid-based cancer biomarkers—microRNAs (miRNAs)—by high intensity focused ultrasound (HIFU) was investigated in a rat prostate cancer model. The benefits of three different HIFU treatment protocols causing localized tissue lysis (histotripsy), bubble-induced reversible permabilization (cavitation), or mild hyperthermia in stimulation of miRNA release were compared to untreated controls” (emphasis added)),
the electronic controller being further configured to control application of non-thermal histotripsy treatment with the histotripsy therapy transducer array to the at least one target tumor according to the treatment plan to mechanically lyse and solubilize tumor cells to release the tumor antigens (see, e.g., Para. [0037], “The ultrasound source 400 can be an ultrasound transducer that emits high levels of ultrasound energy toward a focus 485. The focus 485 can be a point, plane, region, or volume at which the intensity of the ultrasound energy emitted by the ultrasound source 400 is the highest. For example, the ultrasound source 400 generally has a focal depth equal to the diameter of the ultrasound transducer. The function generator 100 and the amplifier 200 can drive the ultrasound source 400 to radiate HIFU waves that induce boiling bubbles or cavitation proximate to the focus 485 to mechanically disrupt (e.g., reversibly disrupt or damage) the tissue mass or suspected tissue mass” (emphasis added), and Para. [0044-0046], and Para. [0070], “The ability of ultrasound to stimulate the release of cancer-specific protein biomarkers into the circulation was recently reported, however, physical and biological mechanisms behind it are unclear. In addition, the protein biomarker in that study (carcinoembryonic antigen, CEA) is expressed on the cell surface, thus providing no proof of principal for releasing biomarker molecules from within the cell. Here, the release of a recently established class of intracellular nucleic acid-based cancer biomarkers—microRNAs (miRNAs)—by high intensity focused ultrasound (HIFU) was investigated in a rat prostate cancer model. The benefits of three different HIFU treatment protocols causing localized tissue lysis (histotripsy), bubble-induced reversible permabilization (cavitation), or mild hyperthermia in stimulation of miRNA release were compared to untreated controls” (emphasis added)).
Regarding claim 2, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet further discloses the system further comprising an evaluation device (see, e.g., Para. [0039] and [0041-0043]) configured to evaluate an immune response of the lysed and solubilized tumor cells (see, e.g., Para. [0069], “The levels of these miRNAs were elevated up to 30-fold within minutes after the ultrasound procedure, and then declined over the course of several hours. The effects on tissue were evaluated in the resected tumors, and only micron-sized areas of hemorrhage scattered through otherwise intact tissue were found when the HIFU was applied as a cavitation regime, suggesting damage to small capillaries. Liquefaction HIFU caused substantial disruption to the tissue in corollary experiments. These data provided the proof of principle for the technology disclosed herein directed to “ultrasound-aided liquid molecular biopsy””).
Regarding claim 3, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet further discloses wherein the cell response includes immunogenic cell death, infiltration of inflammatory and antigen presenting cells, infiltration and activation of T cells, increased tumor-specific T cells, infiltration of natural killer cells, B cells and CD4+ T cells, and/or depletion of immunosuppressive regulatory T cells and myeloid-derived suppressor cells (see, e.g., Para. [0037], “The ultrasound source 400 can be an ultrasound transducer that emits high levels of ultrasound energy toward a focus 485. The focus 485 can be a point, plane, region, or volume at which the intensity of the ultrasound energy emitted by the ultrasound source 400 is the highest. For example, the ultrasound source 400 generally has a focal depth equal to the diameter of the ultrasound transducer. The function generator 100 and the amplifier 200 can drive the ultrasound source 400 to radiate HIFU waves that induce boiling bubbles or cavitation proximate to the focus 485 to mechanically disrupt (e.g., reversibly disrupt or damage) the tissue mass or suspected tissue mass” (emphasis added), and Para. [0044-0046], and Para. [0070], “The ability of ultrasound to stimulate the release of cancer-specific protein biomarkers into the circulation was recently reported, however, physical and biological mechanisms behind it are unclear. In addition, the protein biomarker in that study (carcinoembryonic antigen, CEA) is expressed on the cell surface, thus providing no proof of principal for releasing biomarker molecules from within the cell. Here, the release of a recently established class of intracellular nucleic acid-based cancer biomarkers—microRNAs (miRNAs)—by high intensity focused ultrasound (HIFU) was investigated in a rat prostate cancer model. The benefits of three different HIFU treatment protocols causing localized tissue lysis (histotripsy), bubble-induced reversible permabilization (cavitation), or mild hyperthermia in stimulation of miRNA release were compared to untreated controls” (emphasis added)).
Regarding claim 11, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet further discloses wherein the at least one target tumor (volume of tissue 112) is located in a group consisting of a liver, a kidney, a spleen, a pancreas, a colorectal, a bowel, a stomach, an esophagus, a breast, a lung, a head, a neck, a thyroid, skin, nervous tissue, hematological malignancies, a sarcoma, primary and metastatic lesions, and brain tissue (see, e.g., Para. [0045], “In operation, the ultrasound source 400 is positioned proximate to a volume of tissue 112 (e.g., an organ), and the focus 485 of the ultrasound source 400 is aligned with a target site within the tissue 112 using the positioning device 110. For example, the ultrasound source 400 can be positioned such that its focus 485 is a depth within an ex vivo or in vivo liver, kidney, heart, and/or other tissue mass and aligned with a tumor, cancerous tissue region, and/or other volume of tissue that a clinician would like to mechanically damage”).
Claim Rejections - 35 USC § 103
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 4-5 and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Chevillet (US 2017/0071515 A1), as applied to claim 1 above, in view of Cannata et al. (US 2020/0164231 A1, with effectively filed date 11/28/2018, hereinafter Cannata).
Regarding claim 4, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet does not specifically disclose wherein the treatment volume of the at least one target tumor ranges from 25% to 90% of a volume of the at least one target tumor.
However, in the same field of endeavor of histotripsy, Cannata discloses wherein the treatment volume of the at least one target tumor ranges from 25% to 90% of a volume of the at least one target tumor (see, e.g., Para. [0206], lines 1-4, “histotripsy therapy can be applied in a “radial spiral” pattern that minimizes the distance between treatment columns while maintaining an “inside-out” lesion development in tissue”, and Para. [0208], lines 1-7, “FIGS. 11B and 11C illustrate additional side and top views of a radial spiral pattern, showing how each of the individual planned bubble cloud treatments fills the target tissue volume. It can be seen from these images that the radial spiral pattern covers nearly the entire tissue volume. In some embodiments, the radial spiral pattern can be implemented to cover 90-100% of the target tissue volume”, where it is disclosed that 90% of the target tissue volume can be treated with the histotripsy therapy using a radial spiral pattern, which is a percentage in the claimed range).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the treatment volume of the at least one target tumor ranges from 25% to 90% of a volume of the at least one target tumor, as disclosed by Cannata. One of ordinary skill in the art would have been motivated to make this modification in order to desirably apply the histotripsy therapy/treatment, and in order to reduce treatment times by utilizing a specific application technique/pattern, as recognized by Cannata (see, e.g., Para. [0206-0208]).
Regarding claim 5, Chevillet modified by Cannata discloses the histotripsy therapy system of claim 4, as set forth above. Chevillet does not specifically disclose wherein the treatment volume of the at least one target tumor is at least 1cm^3 in volume.
However, in the same field of endeavor of histotripsy, Cannata discloses wherein the treatment volume of the at least one target tumor is at least 1cm^3 in volume (see, e.g., Para. [0203], lines 1-18, “The “Standard Z Side-Side” and “Standard Z Shuffle” patterns represent variations of the SZ pattern. The spherical volume is still traversed in a set of axial slices parallel to the imaging plane, and the progression of treatment within each slice remains the same… The “Standard Z Shuffle” pattern increments through slices in a strategic order selected to maximize the spatial distribution of successive treatment slices. If the center axial slice of the sphere is defined as slice 0, the slice farthest in the +x-dimension as 6, and the slice farthest in the −x-dimension as −6, then the “Standard Z Shuffle” progresses through the 13 slices comprising the 3 cm sphere”, as well as Para. [0199-0202] and Figs. 7A-7B, where the diameter of the sphere/treatment volume that is receiving the histotripsy treatment is disclosed to be 3cm, and therefore, the volume of the disclosed sphere can be calculated as being 4.5*pi cm^3 or approximately 14.1 cm^3 (i.e., volume calculated by taking the radius of 1.5cm to the third power, then multiplied by 4/3 and multiplied by pi), which is greater than/at least 1cm^3 in volume).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the histotripsy therapy system of Chevillet modified by Cannata by including wherein the treatment volume of the at least one target tumor is at least 1cm^3 in volume, as disclosed by Cannata. One of ordinary skill in the art would have been motivated to make this modification in order to desirably apply the histotripsy therapy/treatment, and in order to improve treatment patterns within tissue that can reduce treatment time, improve efficacy, and reduce the amount of energy and prefocal tissue heating delivered to patients, as recognized by Cannata (see, e.g., Para. [0199-0203]).
Regarding claim 12, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet does not specifically disclose wherein the treatment location comprises only a central portion of the at least one target tumor.
However, in the same field of endeavor of histotripsy, Cannata discloses wherein the treatment location comprises only a central portion of the at least one target tumor (see, e.g., Para. [0027], lines 1-4, “the method further comprises repeating the steps at six or more test locations in the tissue. The six or more test locations may be positioned in cubic coordinates around a center of said target location”, and Para. [0187], lines 1-14, “As a part of planning or during the treatment, the software (and in working with other components of the system) may allow the user to evaluate and test acoustic cavitation/histotripsy thresholds at various locations in a user-selected region of interest or defined treatment area/volume, to determine the minimum cavitation thresholds throughout said region or area/volume, to ensure treatment parameters are optimized to achieve, maintain and dynamically control acoustic cavitation/histotripsy. In one embodiment, the system allows a user to manually evaluate and test threshold parameters at various points. Said points may include those at defined boundary, interior to the boundary and center locations/positions, of the selected region of interest and treatment area/volume”, where the disclosed histotripsy treatment may be applied at locations/positions at the center of the target location/volume).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the treatment location comprises only a central portion of the at least one target tumor, as disclosed by Cannata. One of ordinary skill in the art would have been motivated to make this modification in order to desirably apply the histotripsy therapy/treatment, and in order to improve treatment patterns within tissue that can reduce treatment time, improve efficacy, and reduce the amount of energy and prefocal tissue heating delivered to patients, as recognized by Cannata (see, e.g., Para. [0199-0203]).
Regarding claim 13, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet does not specifically disclose wherein the treatment location comprises only a periphery of the at least one target tumor.
However, in the same field of endeavor of histotripsy, Cannata discloses wherein the treatment location comprises only a periphery of the at least one target tumor (see, e.g., Para. [0187], lines 1-14, “As a part of planning or during the treatment, the software (and in working with other components of the system) may allow the user to evaluate and test acoustic cavitation/histotripsy thresholds at various locations in a user-selected region of interest or defined treatment area/volume, to determine the minimum cavitation thresholds throughout said region or area/volume, to ensure treatment parameters are optimized to achieve, maintain and dynamically control acoustic cavitation/histotripsy. In one embodiment, the system allows a user to manually evaluate and test threshold parameters at various points. Said points may include those at defined boundary, interior to the boundary and center locations/positions, of the selected region of interest and treatment area/volume”, where the disclosed histotripsy treatment may be applied at locations/positions at the defined boundary/periphery of the target location/volume).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the treatment location comprises only a periphery of the at least one target tumor, as disclosed by Cannata. One of ordinary skill in the art would have been motivated to make this modification in order to desirably apply the histotripsy therapy/treatment, and in order to improve treatment patterns within tissue that can reduce treatment time, improve efficacy, and reduce the amount of energy and prefocal tissue heating delivered to patients, as recognized by Cannata (see, e.g., Para. [0199-0203]).
Regarding claim 14, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet does not specifically disclose wherein the treatment location comprises a plurality of programmed treatment locations distributed spatially through the at least one target tumor.
However, in the same field of endeavor of histotripsy, Cannata discloses wherein the treatment location comprises a plurality of programmed treatment locations distributed spatially through the at least one target tumor (see, e.g., Para. [0187-0188] and [0199-0209] with Figs. 7A-7B and 11B-11E, where it is disclosed that treatment patterns can be utilized to apply the treatment throughout nearly the entire tissue volume, in which the volume is divided into a number of slices for receiving treatment, and where the “slices” of the treatment patterns correspond to each of the claimed plurality of programmed treatment locations distributed spatially through the target tumor).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the treatment location comprises a plurality of programmed treatment locations distributed spatially through the at least one target tumor, as disclosed by Cannata. One of ordinary skill in the art would have been motivated to make this modification in order to desirably apply the histotripsy therapy/treatment, and in order to improve treatment patterns within tissue that can reduce treatment time, improve efficacy, and reduce the amount of energy and prefocal tissue heating delivered to patients, as recognized by Cannata (see, e.g., Para. [0199-0203]).
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Chevillet (US 2017/0071515 A1), as applied to claims 1-2 above, in view of Davalos et al. (US 2019/0282294 A1, of record, hereinafter Davalos ‘294).
Regarding claim 6, Chevillet discloses the histotripsy therapy system of claim 2, as set forth above. Chevillet does not specifically disclose wherein the evaluation device is configured to provide an assessment of immunological cell death and/or immune activation.
However, in the same field of endeavor of histotripsy and non-thermal ablation, Davalos ‘294 discloses wherein the evaluation device is configured to provide an assessment of immunological cell death and/or immune activation (see, e.g., Para. [0090], lines 1-8, “The downstream treatment regimen can optionally be or include measuring an immune response in the subject at one or more time points post non-thermal ablation treatment. In some aspects, the activation/promotion of the immune response can be evaluated by monitoring the reduction in immunosuppressive immune molecules and/or increase in pro-inflammatory molecules on the local and systemic level”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the evaluation device is configured to provide an assessment of immunological cell death and/or immune activation, as disclosed by Davalos ‘294. One of ordinary skill in the art would have been motivated to make this modification in order to accurately and desirably monitor/measure/evaluate the immune response after the desired non-thermal ablation treatment, as recognized by Davalos ‘294 (see, e.g., Para. [0090]).
Regarding claim 7, Chevillet discloses the histotripsy therapy system of claim 2, as set forth above. Chevillet does not specifically disclose wherein the evaluation device comprises a tissue biopsy device.
However, in the same field of endeavor of histotripsy and non-thermal ablation, Davalos ‘294 discloses wherein the evaluation device comprises a tissue biopsy device (see, e.g., Para. [0090], lines 1-21, “The downstream treatment regimen can optionally be or include measuring an immune response in the subject at one or more time points post non-thermal ablation treatment. In some aspects, the activation/promotion of the immune response can be evaluated by monitoring the reduction in immunosuppressive immune molecules and/or increase in pro-inflammatory molecules on the local and systemic level… These immune molecules and/or cells can be measured in biopsy or other tissue and/or a bodily fluid (e.g. blood, saliva, urine, breast milk)”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the evaluation device comprises a tissue biopsy device, as disclosed by Davalos ‘294. One of ordinary skill in the art would have been motivated to make this modification in order to accurately and desirably monitor/measure/evaluate the immune response after the desired non-thermal ablation treatment, as recognized by Davalos ‘294 (see, e.g., Para. [0090]).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Chevillet (US 2017/0071515 A1), as applied to claim 1 above, in view of Davalos et al. (US 2018/0161086 A1, of record, hereinafter Davalos ‘086).
Regarding claim 8, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet does not specifically disclose wherein the medical imaging modality comprises CT, MRI, and/or PET imaging.
However, in the same field of endeavor of non-thermal ablation, Davalos ‘086 discloses wherein the medical imaging modality comprises CT, MRI, and/or PET imaging (see, e.g., Para. [0104], lines 1-19, “The advantages of electric pulse therapies over other ablation techniques lay within their ability to kill tissue through a non-thermal mechanism… application of the procedure can be monitored in real-time using ultrasound and confirmed with both ultrasound and MRI, among other imaging techniques. The methods of the invention allow for killing of target cells and tissues, and exhibit rapid lesion creation and resolution, prompting the repopulation of the region with healthy cells. Though treatment success is not dependent upon the immune system, a tumor specific immune response capable of helping to destroy any residual micro-metastases occurs when the invention is practiced to kill tumor cells, decreasing the chances of recurrence”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the medical imaging modality comprises CT, MRI, and/or PET imaging, as disclosed by Davalos ‘086. One of ordinary skill in the art would have been motivated to make this modification in order to accurately and desirably monitor the non-thermal ablation procedure, as recognized by Davalos ‘086 (see, e.g., Para. [0104]).
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Chevillet (US 2017/0071515 A1), as applied to claim 1 above, in view of Onik et al. (US 2019/0023804 A1, of record, hereinafter Onik).
Regarding claim 9, Chevillet discloses the histotripsy therapy system of claim 1, as set forth above. Chevillet does not specifically disclose wherein the histotripsy therapy system is configured to elicit an immune response in at least one distant tumor of a same phenotype as the at least one target tumor.
However, in the same field of endeavor of checkpoint inhibitors and non-thermal ablation treatments, Onik discloses wherein the histotripsy therapy system is configured to elicit an immune response in at least one distant tumor of a same phenotype as the at least one target tumor (see, e.g., Para. [0065], lines 1-14, “Metastatic tumors can be treated using methods described herein. For example, performing a treatment method described herein on a tumor located at one site in the subject's body (e.g., a primary tumor), can stimulate the subject's immune defenses against the tumor and cause an immune attack on tumors of the same or even different type of at another site(s) in the subject's body (e.g., a metastatic tumor). A metastatic tumor can arise from a multitude of primary tumor types, including but not limited to those of prostate, colon, lung, breast, bone, and liver origin. Metastases develop, e.g., when tumor cells shed from a primary tumor adhere to vascular endothelium, penetrate into surrounding tissues, and grow to form independent tumors at sites separate from a primary tumor”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the histotripsy therapy system of Chevillet by including wherein the histotripsy therapy system is configured to elicit an immune response in at least one distant tumor of a same phenotype as the at least one target tumor, as disclosed by Onik. One of ordinary skill in the art would have been motivated to make this modification in order to provide the desired treatment to metastatic/distant tumors along with the treatment of a primary tumor, as recognized by Onik (see, e.g., Para. [0034] and [0065]).
Regarding claim 10, Chevillet modified by Onik discloses the histotripsy therapy system of claim 9, as set forth above. Chevillet does not specifically disclose wherein the at least one distant tumor is located in a different organ or anatomical location than the at least one target tumor.
However, in the same field of endeavor of checkpoint inhibitors and non-thermal ablation treatments, Onik discloses wherein the at least one distant tumor is located in a different organ or anatomical location than the at least one target tumor (see, e.g., Para. [0065], lines 1-14, “Metastatic tumors can be treated using methods described herein. For example, performing a treatment method described herein on a tumor located at one site in the subject's body (e.g., a primary tumor), can stimulate the subject's immune defenses against the tumor and cause an immune attack on tumors of the same or even different type of at another site(s) in the subject's body (e.g., a metastatic tumor). A metastatic tumor can arise from a multitude of primary tumor types, including but not limited to those of prostate, colon, lung, breast, bone, and liver origin. Metastases develop, e.g., when tumor cells shed from a primary tumor adhere to vascular endothelium, penetrate into surrounding tissues, and grow to form independent tumors at sites separate from a primary tumor”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the histotripsy therapy system of Chevillet modified by Onik by including wherein the at least one distant tumor is located in a different organ or anatomical location than the at least one target tumor, as disclosed by Onik. One of ordinary skill in the art would have been motivated to make this modification in order to provide the desired treatment to metastatic/distant tumors along with the treatment of a primary tumor, as recognized by Onik (see, e.g., Para. [0034] and [0065]).
Response to Arguments
Applicant's arguments, see Remarks filed 11/20/2025, have been fully considered but they are not persuasive.
Regarding Chevillet et al. (US 2017/0071515 A1), Applicant argues that Chevillet does not contemplate or disclose deriving a treatment plan with an optimal treatment volume for a given tumor to increase the immune response of releasing tumor antigens.
Examiner respectfully disagrees and emphasizes that Chevillet discloses an electronic controller (controller 300) (see, e.g., Para. [0039] and [0041-0043]) configured to derive a treatment plan that includes an optimal treatment volume of the at least one target tumor to be treated that will increase a cell response of releasing tumor antigens based at least in part on the image, a location of the target tumor, or a tissue type of the target tumor (see, e.g., Para. [0028], “Systems and methods configured in accordance with embodiments of the present technology are expected to provide effective minimally invasive (e.g., non-invasive) diagnosis and/or treatment of tissue masses, and facilitate better informed, potentially personalized treatment related decisions while reducing risks commonly associated with conventional methods such as needle biopsy” (emphasis added), and Para. [0037], “The ultrasound source 400 can be an ultrasound transducer that emits high levels of ultrasound energy toward a focus 485. The focus 485 can be a point, plane, region, or volume at which the intensity of the ultrasound energy emitted by the ultrasound source 400 is the highest. For example, the ultrasound source 400 generally has a focal depth equal to the diameter of the ultrasound transducer. The function generator 100 and the amplifier 200 can drive the ultrasound source 400 to radiate HIFU waves that induce boiling bubbles or cavitation proximate to the focus 485 to mechanically disrupt (e.g., reversibly disrupt or damage) the tissue mass or suspected tissue mass” (emphasis added), and Para. [0057], “the transducer head 420 has a generally concave shape, providing an array of transducer elements 425 in a generally concave pattern. The resulting amplified ultrasound energy waveform 480 provided by the ultrasound source 400 includes a focal point 485 located a predetermined focal distance D from the ultrasound source 400. The focal distance D may be selected to correspond to the location (e.g., depth) of a tissue mass or suspected tissue mass T, such that the focal point 485 is located within the tissue mass or suspected tissue mass T of a patient P”, where the focus/focal point 485 corresponds to an optimal volume and location of the target tumor that receives treatment, and where the focus/focal point 485 is selected such that “the intensity of the ultrasound energy emitted by the ultrasound source 400 is the highest”, as stated in Para. [0037], and therefore a cell response resulting from the treatment of the highest intensity of the ultrasound energy being emitted would be increased compared to a lower intensity of emitted ultrasound energy, and Para. [0070], “The ability of ultrasound to stimulate the release of cancer-specific protein biomarkers into the circulation was recently reported, however, physical and biological mechanisms behind it are unclear. In addition, the protein biomarker in that study (carcinoembryonic antigen, CEA) is expressed on the cell surface, thus providing no proof of principal for releasing biomarker molecules from within the cell. Here, the release of a recently established class of intracellular nucleic acid-based cancer biomarkers—microRNAs (miRNAs)—by high intensity focused ultrasound (HIFU) was investigated in a rat prostate cancer model. The benefits of three different HIFU treatment protocols causing localized tissue lysis (histotripsy), bubble-induced reversible permabilization (cavitation), or mild hyperthermia in stimulation of miRNA release were compared to untreated controls” (emphasis added)).
Therefore, Chevillet does disclose each and every feature of the independent claim 1, as set forth above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/T.D./Examiner, Art Unit 3798
/PASCAL M BUI PHO/Supervisory Patent Examiner, Art Unit 3798
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