CTNF 19/136,218 CTNF 94546 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Specification The abstract of the disclosure is objected to because legalese, claim language is used. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 07-20-aia AIA 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. 07-21-aia AIA Claim s 1-11 and 23-30 are rejected under 35 U.S.C. 103 as being unpatentable over Khokhlova et. al. (U.S. 20200353293, November 12, 2020)(hereinafter, “Khokhlova”) in view of Bawiec et. al. (“A prototype system for boiling histotripsy in abdominal targets based on a 256-element spiral array”. 2021)(hereinafter, “Bawiec” ) . Regarding Claim 1 , Khokhlova teaches: A method for an ultrasound treatment using high intensity focused ultrasound (HIFU) (“…a method for a transrectal ultrasound treatment uses high intensity focused ultrasound (HIFU).” (Abstract); “Example devices, methods, and systems are described herein.” [0035]; “…a system for transrectal ultrasound boiling histotripsy…” [0036]), the method comprising: generating boiling histotripsy (BH) therapy ultrasound with a therapy transducer (“…generating a boiling histotripsy (BH) therapy ultrasound by a therapy transducer in a frequency range of 1 MHz to 2.8 MHz and a surface intensity range of 10 W/cm2 to 80 W/cm2, where the therapy transducer is about 50 mm long and about 35 mm wide…” [0009]; “…a system for transrectal ultrasound boiling histotripsy ablation in accordance with an embodiment of the present technology. An ultrasound system 1000 includes an ultrasound probe 100 having a therapy transducer and optionally an imaging transducer.” [0036]); applying the therapy ultrasound by directing a plurality of ultrasound pulses having ultrasound shock waves to a target tissue (“…applying the therapy ultrasound by directing ultrasound pulses having ultrasound shock waves to a target tissue at a focal depth of 2.5 cm to 5.5 cm…” [0009]; “… the therapy transducer 12 generates ultrasound shocks of about 60-140 MPa in a target tissue located at a focal region about 35-55 mm away from the transducer.” [0040]); generating at least one pm-scale vapor bubble at the target tissue within each pulse (“…generating at least one μm-scale vapor bubble at a target region…” [0009]); growing the at least one vapor bubble to at least one mm-scale bubble (“… growing the at least one vapor bubble to at least one mm-scale bubble…” [0009]; “… FIG. 7B, which shows an initially generated vapor bubble 64 at μm-scale growing into a mm-scale gas bubble 74.” [0048]); and mechanically disintegrating the target tissue by interactions between the ultrasound shock waves with the at least one mm-scale bubble and bubble clouds, wherein the interactions take place within a duration of individual ultrasound pulses of the plurality of ultrasound pulses (“…mechanically disintegrating a surrounding tissue by interactions between the at least one mm-scale bubble and the ultrasound shock waves within a pulse.” [0009]; “…the pulses of HIFU may extends over 1-20 ms, followed by a pause of 0.1-2 second.” [0048]). Khokhlova does not teach: moving a focal point during each pulse of the plurality of pulses from a first region of the target tissue to a second region of the target tissue. Bawiec in the field of histotripsy systems teaches: “In order to change the position of the focus of the HIFU transducer array, electronic beam steering was implemented by choosing additional time delays for each individual element so that the arrival time of the wave from each element was the same at the target location. This enabled steering of the HIFU focus both laterally and axially.” (Materials and Methods: experimental arrangements); “These tests showed that achieving uniform volumetric tissue liquefaction required that individual focus locations had to be spaced no more than 1 mm laterally and 5 mm axially, and at least 5 BH pulses had to be delivered per focal point.” (Discussions) Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Khokhlova to move a focal point during each pulse of the plurality of pulses from a first region of the target tissue to a second region of the target tissue as taught in Bawiec to improve system reliability (Bawiec, Introduction). Regarding Claim 2 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein the plurality of pulses has a duration of 1-20ms (“…the BH pulses have 5 ms duration, 2 Hz pulse repetition frequency, and 20 pulses/focus.” [0008]; “…the pulses of HIFU may extends over 1-20 ms, followed by a pause of 0.1-2 second.” [0048]). Regarding Claim 3 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein the therapy transducer operates in a frequency range of 1 MHz to 20 MHz (“…a frequency range of 1 MHz to 2.8 MHz…” [0009]). Regarding Claim 4 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein the therapy transducer is moved between a plurality of regions, including the first region and the second region. Bawiec in the field of histotripsy systems teaches: “With the intent of treating a volume, automated scripts steered the focus over planar trajectories, with larger volumes including multiple treatment planes spaced 5 mm apart along the beam axis. In each plane, trajectories comprised multiple concentric circles with radii of 2 mm, 4 mm, and 6 mm. Within each circle, the tangential spacing between target sites was approximately 1.5 mm…” (Materials and Methods: Gel Phantom Experiments). Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the combination such that the therapy transducer is moved between a plurality of regions, including the first region and the second region as taught in Bawiec to improve system reliability (Bawiec, Introduction). Regarding Claim 5 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein the second region is closer to the therapy transducer than the first region. Bawiec in the field of histotripsy systems teaches: “All treatments of the liver were performed with the geometric focus of the array placed 10 mm inside the liver sample. Three planes were treated consecutively beginning with the plane furthest from the transducer. Each focal point in each plane received a single BH pulse before repeating the sonication, for up to 30 total pulses per location (first set) or up to 10 pulses per location (second set).” …” (Materials and Methods: Liver Experiments Ex Vivo). See Fig. 2 Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the combination such that the second region is closer to the therapy transducer than the first region as taught in Bawiec to improve system reliability (Bawiec, Introduction). Regarding Claim 6 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein a shock amplitude at the focal point of the therapy transducer is in a range of 40MPa to 250MPa (“…a shock amplitude of the therapy ultrasound at a focus depth of 40 mm is about 100 MP…” [0011]; “… the therapy transducer 12 generates ultrasound shocks of about 60-140 MPa in a target tissue located at a focal region about 35-55 mm away from the transducer.” [0040]). Regarding Claim 7 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein the plurality of ultrasound pulses is applied at a focal depth of 0.25 cm to 15 cm (“…applying the therapy ultrasound by directing ultrasound pulses having ultrasound shock waves to a target tissue at a focal depth of 2.5 cm to 5.5 cm…” [0009]). Regarding Claim 8 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein the focal point is moved axially from the first region to the second region. Bawiec in the field of histotripsy systems teaches: “In order to change the position of the focus of the HIFU transducer array, electronic beam steering was implemented by choosing additional time delays for each individual element so that the arrival time of the wave from each element was the same at the target location. This enabled steering of the HIFU focus both laterally and axially.” (Materials and Methods: experimental arrangements); “These tests showed that achieving uniform volumetric tissue liquefaction required that individual focus locations had to be spaced no more than 1 mm laterally and 5 mm axially, and at least 5 BH pulses had to be delivered per focal point.” (Discussions). Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the focal point in the combination to be moved axially from the first region to the second region as taught in Bawiec to improve system reliability (Bawiec, Introduction). Regarding Claim 9 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein the focal point is moved at an angle (“… the phased array therapy transducer 12 may be controlled to provide a range of steering such that the focal area stays within a region limited by at most 80% decrease of the focal intensity.” [0042]). Regarding Claim 10 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein the angle is about 0 to 35 degrees (“…the phased array therapy transducer 12 may be controlled to provide a range of steering such that the focal area stays within a region limited by at most 80% decrease of the focal intensity. In different embodiments, other restrictions to steering angle or depth may be implemented. The illustrated therapy transducer has a central opening with a 15-25 mm diameter (D).” [0042]. See Fig. 5). Regarding Claim 11 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein a Az of the movement of the focal point ranges from 100 to 800 pm. Bawiec in the field of histotripsy systems teaches: “Lateral scans in both the horizontal x and vertical y directions (Fig. 2) were performed with a 200 µm step. For the axial scans along the z direction, a 500 µm step was used. This was done for each steering location in two transverse coordinates in the plane of the geometric focus of the array and axially. Simulations were performed assuming the transducer vibrations are defined by the element design geometry and uniform vibration of each element.” (Materials and Methods: Acoustic Field Characterization with Steering). Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the combination such that Az of the movement of the focal point ranges from 100 to 800 pm as taught in Bawiec to improve system reliability (Bawiec, Introduction). Regarding Claim 23 , A method for an ultrasound treatment using high intensity focused ultrasound (HIFU) (“…a method for a transrectal ultrasound treatment using high intensity focused ultrasound…” [0009]), the method comprising: generating boiling histotripsy (BH) therapy ultrasound with a therapy transducer (“…generating a boiling histotripsy (BH) therapy ultrasound by a therapy transducer in a frequency range of 1 MHz to 2.8 MHz and a surface intensity range of 10 W/cm2 to 80 W/cm2, where the therapy transducer is about 50 mm long and about 35 mm wide…” [0009]; “…a system for transrectal ultrasound boiling histotripsy ablation in accordance with an embodiment of the present technology. An ultrasound system 1000 includes an ultrasound probe 100 having a therapy transducer and optionally an imaging transducer.” [0036]); applying the therapy ultrasound by directing a plurality of ultrasound pulses having ultrasound shock fronts to a target tissue (“…applying the therapy ultrasound by directing ultrasound pulses having ultrasound shock waves to a target tissue at a focal depth of 2.5 cm to 5.5 cm…” [0009]; “… the therapy transducer 12 generates ultrasound shocks of about 60-140 MPa in a target tissue located at a focal region about 35-55 mm away from the transducer.” [0040]); generating at least one pm-scale vapor bubble at the target tissue during each pulse (“…generating at least one μm-scale vapor bubble at a target region…” [0009]); growing the at least one vapor bubble to at least one mm-scale bubble (“… growing the at least one vapor bubble to at least one mm-scale bubble…” [0009]; “… FIG. 7B, which shows an initially generated vapor bubble 64 at μm-scale growing into a mm-scale gas bubble 74.” [0048]); and mechanically disintegrating the target tissue by interactions between the ultrasound shock waves with the at least one mm-scale bubble and bubble clouds, wherein the interactions take place within a duration of individual ultrasound pulses of the plurality of ultrasound pulses (“…mechanically disintegrating a surrounding tissue by interactions between the at least one mm-scale bubble and the ultrasound shock waves within a pulse.” [0009]; “…the pulses of HIFU may extends over 1-20 ms, followed by a pause of 0.1-2 second.” [0048]). Khokhlova does not teach: moving a focal point of each pulse of the plurality of pulses between a plurality of regions of the target tissue. Bawiec in the field of histotripsy systems teaches: “In order to change the position of the focus of the HIFU transducer array, electronic beam steering was implemented by choosing additional time delays for each individual element so that the arrival time of the wave from each element was the same at the target location. This enabled steering of the HIFU focus both laterally and axially.” (Materials and Methods: experimental arrangements); “These tests showed that achieving uniform volumetric tissue liquefaction required that individual focus locations had to be spaced no more than 1 mm laterally and 5 mm axially, and at least 5 BH pulses had to be delivered per focal point.” (Discussions) Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Khokhlova to move a focal point during each pulse of the plurality of pulses from a first region of the target tissue to a second region of the target tissue as taught in Bawiec to improve system reliability (Bawiec, Introduction). Regarding Claim 24 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein the plurality of regions is an array of regions corresponding to the target tissue. Regarding Claim 25 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein the method further comprises: sequencing each region in the array of regions; and moving the focal point between each region of the array based on the sequence. Regarding Claim 26 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein the method further comprises: applying a number of pulses at each region of the array of regions, wherein the number of pulses differs between each region of the array of regions. Regarding Claim 27 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova does not teach: wherein the focal point is moved axially. Bawiec in the field of histotripsy systems teaches: “In order to change the position of the focus of the HIFU transducer array, electronic beam steering was implemented by choosing additional time delays for each individual element so that the arrival time of the wave from each element was the same at the target location. This enabled steering of the HIFU focus both laterally and axially.” (Materials and Methods: experimental arrangements); “These tests showed that achieving uniform volumetric tissue liquefaction required that individual focus locations had to be spaced no more than 1 mm laterally and 5 mm axially, and at least 5 BH pulses had to be delivered per focal point.” (Discussions) Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the focal point in the combination to be moved axially from the first region to the second region as taught in Bawiec to improve system reliability (Bawiec, Introduction). Regarding Claim 28 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein a shock amplitude at the focal point of the therapy transducer is in a range of 40MPa to 250MPa (“…applying the therapy ultrasound by directing ultrasound pulses having ultrasound shock waves to a target tissue at a focal depth of 2.5 cm to 5.5 cm…” [0009]; “… the therapy transducer 12 generates ultrasound shocks of about 60-140 MPa in a target tissue located at a focal region about 35-55 mm away from the transducer.” [0040]). Regarding Claim 29 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein the plurality of ultrasound pulses is applied at a focal depth of 0.25 cm to 15 cm (“…applying the therapy ultrasound by directing ultrasound pulses having ultrasound shock waves to a target tissue at a focal depth of 2.5 cm to 5.5 cm…” [0009]). Regarding Claim 30 , the combination of Khokhlova and Bawiec teach the claim limitations as noted above. Khokhlova further teaches: wherein the focal point is moved at an angle (“… the phased array therapy transducer 12 may be controlled to provide a range of steering such that the focal area stays within a region limited by at most 80% decrease of the focal intensity.” [0042]) . Conclusion 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Xu et. al. U.S. 20210252313 teaches a histotripsy immunosensitization system . Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMAL FARAG whose telephone number is (571)270-3432. The examiner can normally be reached 8:30 - 5:30 M-F. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Keith Raymond can be reached at (571) 270-1790. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AMAL ALY FARAG/Primary Examiner, Art Unit 3798 Application/Control Number: 19/136,218 Page 2 Art Unit: 3798 Application/Control Number: 19/136,218 Page 3 Art Unit: 3798 Application/Control Number: 19/136,218 Page 4 Art Unit: 3798 Application/Control Number: 19/136,218 Page 5 Art Unit: 3798 Application/Control Number: 19/136,218 Page 6 Art Unit: 3798 Application/Control Number: 19/136,218 Page 7 Art Unit: 3798 Application/Control Number: 19/136,218 Page 8 Art Unit: 3798 Application/Control Number: 19/136,218 Page 9 Art Unit: 3798 Application/Control Number: 19/136,218 Page 10 Art Unit: 3798 Application/Control Number: 19/136,218 Page 11 Art Unit: 3798 Application/Control Number: 19/136,218 Page 12 Art Unit: 3798 Application/Control Number: 19/136,218 Page 13 Art Unit: 3798
Prosecution Insights