DETAILED ACTION
This office action is in response to the communication received on 10/21/2025 concerning application no. 18/214,421 filed on 06/26/2023.
Claims 1-20 are pending.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant's arguments filed 10/21/2025 have been fully considered but they are not persuasive.
Regarding the 103 rejection, Applicant argues that the one with ordinary skill in the art would understand that a single element transducer can emit and diverged, convergent, and planar waves. Applicant argues that Aubry uses the use of multiple elements in the generation of the focus. Applicant argues that the specification teaches the use of a lens and how the transducer elements can be a concave surface.
Examiner disagrees. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the use of single element transducers, lens, and/or a concave surface) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Nowhere in the claims is it established that the transducer is a single element transducer. Assuming, arguendo, such an element was present, Applicant’s remarks are unpersuasive. Applicant’s remark that “The Applicant respectfully disagrees with the article recited by the examiner (https ://radiopaedia.org/articles/beam-focusing?lang=us), which describes single-element ultrasound transducers but does not indicate that "all" single-element ultrasound transducers are fixed focused transducers” is conclusory and without support. If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. See, e.g., In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc). Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by counsel, In re Chu, 66 F.3d 292, 299, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995), or by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984). However, arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). A single element cannot operate alone in generating a focus. It is well-known in the art that focusing is “is analogous to using a magnifying glass to focus beams of sunlight on a single point to burn a hole in a leaf. With focused ultrasound, an acoustic lens is used to concentrate multiple intersecting beams of ultrasound on a target deep in the body with extreme precision and accuracy.”1 Focusing requires a plurality of beams as a singular beam does not have a focal point as it is a form of sound in the context of ultrasound. Ultrasound focusing can be performed by beamforming2 or via an acoustic lens as the evidentiary citation above notes. Focusing requires the ability to “concentrate multiple sound waves on a point in the body”3 and that cannot be performed via a single transducer element as it would be emitting a single ultrasound beam emission. Even multiple pulses from the same element would be unable to focus given that the timing of transmission would be spaced apart and the attenuation conditions remain constant. Even with the Radiopedia citation, Applicant provided no explanation on how it was deficient. Furthermore, the Radiopedia citation clearly notes that with regards to transmit focusing “this occurs by adding a time delay to the firing of each of the piezoelectric elements” (emphasis added)4. MPEP 716.01(c) establishes “Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984).” Aubry teaches the focusing via a transducer as required by the claim as paragraph 0119 teaches that each individual signal of the transducers is determined and obtained for the purpose of ensuring accurate focusing. Paragraph 0086 teaches the use of the sub-arrays for the individualized emission. Assuming, arguendo, Aubry was deficient, the idea of “at least one ultrasound transducer of the ultrasound transducer array is configured to emit a focused acoustic wave” is not novel. At least Hynynen et al. (PGPUB No. US 2019/0021666), Liu et al. (PGPUB No. US 2012/0271165), Zeng et al. (PGPUB No. US 2012/0209150), Hynynen et al. (PGPUB No. US 2022/0233890), Hynynen et al. (PGPUB No. US 2002/0038086), Hynynen et al. (PGPUB No. US 2004/0210134), and Zachar et al. (US Patent No. 12,179,042) teach the commonly known principle of ultrasound focusing. It is so well-known it is taught as a “Basics of Ultrasound” where it is taught as “Focus concentrates the ultrasound waves at a specific depth to sharpen the resolution.”5
Examiner maintains the rejection.
Applicant's arguments filed 10/21/2025 have been fully considered but they are not persuasive.
Regarding the double patenting, “The Office Action rejects certain claims on the ground of nonstatutory double patenting to U.S. Patent No. 11,730,980, US Patent No. 11,975,156, and US Appl. No. 18/648,807. Applicant respectfully requests that the double patenting rejections be held until an agreement is reached on allowable subject matter. Applicant's representative requests that if the Examiner still believes a terminal disclaimer would be appropriate (after reviewing the claim amendments), the Examiner should request that in a future action.”
Examiner disagrees. MPEP 804.I.1 establishes “As filing a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, is necessary for further consideration of the rejection of the claims, such a filing should not be held in abeyance.”
Examiner maintains the rejections. Applicant is encouraged to filed terminal disclaimers to expedite prosecution.
Applicant's arguments filed 10/21/2025 have been fully considered but they are not persuasive.
Applicant in pages 12-13 cites numerous U.S. patents and applications.
It is unclear what Applicant is arguing. The application under review is the instant application. I.e. App. No. 18/214,421. It is unclear if Applicant is trying to have these U.S. patents and applications considered for prosecution. Again, those patents and applications are not reviewed as they are not the claims under consideration. It is unclear if Applicant is trying to create and IDS for consideration. If so, Applicant use the proper means of consideration in the form of an actual IDS and explain how these are relevant to the instant case of App. No. 18/214,421.
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 1-6 and 13-20 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 is indefinite for the following reasons:
Recites “wherein the ultrasound transducer array is configured to emit acoustic waves having an acoustic intensity”. This claim element is indefinite. It would be unclear to one with ordinary skill in the art if the emission is according to the signal that actuates the ultrasound array.
Applicant is encouraged to provide consistent and clear language.
Recites “at least one of ultrasound transducers of the ultrasound transducer array”. There is insufficient antecedent basis for this limitation in the claim.
Recites “at least one of ultrasound transducers of the ultrasound transducer array”. This claim element is indefinite. It would be unclear to one with ordinary skill in the art what the relationships is between the ultrasound transducers and the transducer elements. The claim establishes that the “array comprises a plurality of ultrasound transducer elements”.
Applicant is encouraged to provide consistent and clear language.
Recites “at least one of ultrasound transducers of the ultrasound transducer array”. This claim element is indefinite. Given the above lack of clarity, it would be further unclear to one with ordinary skill in the art if the claim is establishing sub-aperture control or operability according to the array as a whole.
Applicant is encouraged to provide consistent and clear language.
Recites “wherein at least one of ultrasound transducers of the ultrasound transducer array is configured to emit a focused acoustic wave through the skull”. This claim element is indefinite. It would be unclear to one with ordinary skill in the art if this step is the same as the “wherein the ultrasound transducer array is configured to emit acoustic waves having an acoustic intensity” or is different.
Applicant is encouraged to provide consistent and clear language.
Recites “a focused acoustic wave”. This claim element is indefinite. It would be unclear to one with ordinary skill in the art if this focused acoustic wave is of the “acoustic waves” or is a separate and distinct feature.
Applicant is encouraged to provide consistent and clear language.
Claim 13 is indefinite for the following reasons:
Recites “wherein each ultrasound transducer elements of the at least one array of ultrasound transducer elements is configured to emit a focused acoustic wave through the skull”. This claim element is indefinite. It would be unclear to one with ordinary skill in the art if the transducer elements of the array are creating a focused acoustic wave in conjunction with one another or that the element generates the focus acoustic waves.
Applicant is encouraged to provide consistent and clear language.
Recites “modulating a duty-cycle of the signal to cause the focused acoustic waves to have an acoustic intensity with modulated duty cycle”. This claim element is indefinite. It would be unclear to one with ordinary skill in the art in what manner an acoustic intensity can have a modulated duty cycle as a duty cycle is a consideration of time of a signal in which it is active. While the duty cycle may dictate the duration of the acoustic transmission, it does not impact the acoustic intensity that is set by the signal as that is assessed according to amplitude or power.
Applicant is encouraged to provide consistent and clear language.
Claims that are not discussed above but are cited to be rejected under 35 U.S.C. 112(b) are also rejected because they inherit the indefiniteness of the claims they respectively depend upon.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Aubry et al. (PGPUB No. US 2005/0277824) in view of Voorhees et al. (PGPUB No. US 2005/0060012) as evidenced by Galkin ("The Use of Transcranial Focused Ultrasound in CNS Diseases", January 2016, Problems of Neurosurgery, pages 1-108).
Regarding claim 1, Aubry teaches a method of non-invasive ultrasound, comprising:
providing a patient interface configured for coupling to a skin surface of a head of a patient with a brain with tumor cells, the patient interface comprising an ultrasound transducer array and a cooling system (Fig. 1 shows the cap is pressed against the patient head and carried by the robotic arm 4. Paragraph 0078 teaches that the head is positioned securely with the cap. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Fig. 2 shows the rigid cup 11 holding the transducer array 17. Paragraph 0080 teaches the transducers are on the cup 11. Paragraph 0080 teaches that the wall 12 holds a liquid like water. Paragraph 0072 teaches that the system is able to perform hyperthermia treatment. The liquid is used to keep the patient from overheating in such hyperthermia treatments. See Fig. 2),
generating a signal to actuate the ultrasound transducer array (Paragraphs 0087-92 teaches that the electronics rack will control the transducers. See Fig. 3. Paragraph 0079 teaches that the microcomputer controls the transducer arrays), and
wherein the ultrasound transducer array comprises a plurality of ultrasound transducer elements, wherein the ultrasound transducer array is configured to emit acoustic waves having an acoustic intensity (Fig. 2 shows the rigid cup 11 holding the transducer array 17. Paragraph 0080 teaches the transducers are on the cup 11. Paragraph 086 teaches the emission of the sound with consideration to the power levels. Paragraph 0152 teaches the reception of the signal with amplitudes that are used for the ultrasound performance),
wherein at least one of ultrasound transducers of the ultrasound transducer array is configured to emit a focused acoustic wave through the skull (Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain. Paragraph 0119 teaches that each individual signal of the transducers is determined and obtained for the purpose of ensuring accurate focusing. Paragraph 0086 teaches the use of the sub-arrays for the individualized emission),
wherein the patient interface is configured to acoustically couple the ultrasound transducer array to the skin surface (Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain),
wherein the patient interface is configured for conforming to the skin surface (Fig. 2 shows the flexible wall conforming the patient head),
wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies to deliver the focused acoustic waves in the brain at the tumor cells of the patient (Paragraph 0079 teaches that the microcomputer controls the transducer arrays. Paragraph 0115 teaches that the ultrasound waves can be focused to targets in the brain. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Paragraph 0026 teaches that the ultrasound can within a range of frequencies. Paragraph 0103 teaches consideration of the frequency).
However, Aubry is silent regarding a method, comprising:
the cooling system comprising one or more cooling channels comprising independent loops forming a manifold around the skull, the manifold connecting an inlet tube and an outlet tube; and
circulating a fluid through the one or more cooling channels to reduce heat at the head of the patient at the patient interface.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Voorhees teaches a method, comprising:
the cooling system comprising one or more cooling channels comprising independent loops forming a manifold around the skull, the manifold connecting an inlet tube and an outlet tube (Paragraph 0050 teaches the use of a coolant pad that is included in the cooling system. Fig. 7 shows the two matching pads 100a and 100b. Fig. 8 shows the ports 122 and 124 for the pads. Paragraph 0051 teaches that the fluid may be circulated during the use via the fluid ports. Fig. 9 shows the interior of the pad has multiple fluid channels 130 and 140); and
circulating a fluid through the one or more cooling channels to reduce heat at the head of the patient at the patient interface (Paragraph 00007 teaches that the pads have fluid circulating pumps and or temperature regulating systems that are adjusting the temperature of the fluid. This is then allows for the head to be transferred away from the patient. Paragraph 0050 teaches the use of a coolant pad that is included in the cooling system. Fig. 7 shows the two matching pads 100a and 100b. Fig. 8 shows the ports 122 and 124 for the pads. Paragraph 0051 teaches that the fluid may be circulated during the use via the fluid ports. Fig. 9 shows the interior of the pad has multiple fluid channels 130 and 140. Paragraphs 0008-09 teach that the closed system ensures that there is adequate fluid flow paths and that the patient brain has localized cooling).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Voorhees’s teaching of circulating of fluid for temperature control. Galkin provides an evidentiary teaching of the implementation of sonodynamic treatment can be done for neurological conditions and disorders (Pages 99-106 of Galkin). This treatment supplements existing surgical and radiation treatments for CND diseases. Furthermore, this modified method would provide patient with localized cooling for the brain (Paragraph 0008-09 of Voorhees). Furthermore, this modified method allows for the synchronized cooling pads with respect to the ultrasound heating (Paragraph 0057 of Voorhees).
Voorhees, like Aubry, is performing ultrasound transmission in the brain. Voorhees teaches the cooling of the patient head as seen in Fig. 5. Given that the Voorhees teaches the cooling of the head along with ultrasound imaging and also notes that the cooling can be synchronized with the ultrasound heating (Paragraph 0057), it would have been obvious to one with ordinary skill in the art to implement the interior structure of the cooling pad onto the cooling system used in the head of the patient as seen in Fig. 5. This would ensure that the cooling system is able to distribute fluid and normalize fluid flow amongst the channels and synchronization with the ultrasound transmission (Paragraph 0057).
Regarding claim 2, modified Aubry teaches the method in claim 1, as discussed above.
Aubry further teaches a method, further comprising moving the patient interface with respect to the head of the patient (Paragraph 0158 teaches that the cap can be moved via robotic means. Fig. 1-2 show the robotic arm holding the cap in relation to the patient head).
Regarding claim 3, modified Aubry teaches the method in claim 1, as discussed above.
Aubry further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell, and a flexible shell (Paragraph 0080 teaches that the cup 11 is rigid. Cup 11 in Fig. 2. Paragraph 0080 teaches that the cap 2 has a flexible wall 12 that holds a liquid. Wall 12 in Fig. 2. Paragraph 0078 teaches that the cap 2 is controlled by a robotic arm 4. See Fig. 1).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Aubry et al. (PGPUB No. US 2005/0277824) in view of Voorhees et al. (PGPUB No. US 2005/0060012) further in view of Callan et al. (PGPUB No. US 2018/0344872).
Regarding claim 4, modified Aubry teaches the method in claim 1, as discussed above.
However, the combination of Aubry and Voorhees is silent regarding a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Paragraph 0118 teaches the insertion and monitoring of the fluorescence 30 min after the intravenous administration. Paragraph 0173 teaches the ultrasound application for about 3 min after IV administration. Paragraph 0092 teaches transmission from 1 ms to 20 min).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Voorhees with Callan’s teaching of therapy for 30 min to an hour. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Aubry et al. (PGPUB No. US 2005/0277824) in view of Voorhees et al. (PGPUB No. US 2005/0060012) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Liu (PGPUB No. US 2018/0207447).
Regarding claim 5, modified Aubry teaches the method in claim 1, as discussed above.
While Aubry teaches treating cancer (Paragraph 0073), the combination of Aubry and Voorhees is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method,
wherein the sonosensitizer is a porphyrin compound (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS),
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Voorhees with Callan’s teaching of the use of protoporphyrin for SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
However, the combination of Aubry, Voorhees, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry, Voorhees, and Callan with Liu’s teaching of the administration of ALA and the treatment of GBM. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Regarding claim 6, modified Aubry teaches the method in claim 1, as discussed above.
However, Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the ultrasound transducer array comprises a grid of elements, wherein the sonosensitizer is a porphyrin compound,
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2 to activate the sonosensitizer.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Voorhees teaches a method, wherein the ultrasound transducer array comprises a grid of elements (Paragraphs 0028 and 0041 teaches the use of an array of transducers. An array is an arrangement of elements in a grid-like structure).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Voorhees’s teaching of an array of ultrasound. Furthermore, this modified method would provide patient with localized cooling for the brain (Paragraph 0008-09 of Voorhees). Furthermore, this modified method allows for the synchronized cooling pads with respect to the ultrasound heating (Paragraph 0057 of Voorhees).
However, the combination of Aubry and Voorhees is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the sonosensitizer is a porphyrin compound,
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2 to activate the sonosensitizer.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the sonosensitizer is a porphyrin compound (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers),
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site),
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2 to activate the sonosensitizer (Paragraph 0092 teaches of the ultrasound may range from about 0.1 Wcm-2 to about 1 kWcm-2, preferably from about 1 to about 50 Wcm-2).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Voorhees with Callan’s teaching of the use of protoporphyrin for SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
However, the combination of Aubry, Voorhees, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry, Voorhees, and Callan with Liu’s teaching of SDT treatment with ALA and a specific acoustic energy. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claims 7-11 and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Aubry et al. (PGPUB No. US 2005/0277824) in view of Chen (PGPUB No. US 2009/0062724) as supported by Galkin ("The Use of Transcranial Focused Ultrasound in CNS Diseases", January 2016, Problems of Neurosurgery, pages 1-108) further in view of Callan et al. (PGPUB No. US 2018/0344872).
Regarding claim 7, Aubry teaches a method of non-invasive ultrasound, comprising:
providing a non-invasive sonodynamic therapy system configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells (Fig. 1 shows the cap is pressed against the patient head and carried by the robotic arm 4. Paragraph 0078 teaches that the head is positioned securely with the cap. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Fig. 2 shows the rigid cup 11 holding the transducer array 17. Paragraph 0080 teaches the transducers are on the cup 11. Paragraph 0080 teaches that the wall 12 holds a liquid like water. Paragraph 0072 teaches that the system is able to perform hyperthermia treatment. The liquid is used to keep the patient from overheating in such hyperthermia treatments. See Fig. 2),
wherein the non-invasive sonodynamic therapy system comprises:
a patient interface (Fig. 1 shows the cap is pressed against the patient head and carried by the robotic arm 4. Paragraph 0078 teaches that the head is positioned securely with the cap), and
a plurality of ultrasound transducers wherein each of ultrasound transducers of the plurality of ultrasound transducers is configured to emit a focused acoustic wave through the skull (Fig. 2 shows the rigid cup 11 holding the transducer array 17. Paragraph 0080 teaches the transducers are on the cup 11. Paragraph 0080 teaches that the wall 12 holds a liquid like water. Paragraph 0072 teaches that the system is able to perform hyperthermia treatment. The liquid is used to keep the patient from overheating in such hyperthermia treatments. See Fig. 2. Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain. Fig. 2 shows the rigid cup 11 holding the transducer array 17. Paragraph 0080 teaches the transducers are on the cup 11. Paragraph 086 teaches the emission of the sound with consideration to the power levels. Paragraph 0152 teaches the reception of the signal with amplitudes that are used for the ultrasound performance. Paragraph 0079 teaches that the microcomputer controls the transducer arrays. Paragraph 0115 teaches that the ultrasound waves can be focused to targets in the brain. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Paragraph 0026 teaches that the ultrasound can within a range of frequencies. Paragraph 0103 teaches consideration of the frequency);
driving the plurality of ultrasound transducers with a signal (Paragraphs 0087-92 teaches that the electronics rack will control the transducers. See Fig. 3. Paragraph 0079 teaches that the microcomputer controls the transducer arrays);
wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies with the acoustic intensity in the brain at the tumor cells of the patient (Paragraph 0079 teaches that the microcomputer controls the transducer arrays. Paragraph 0115 teaches that the ultrasound waves can be focused to targets in the brain. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Paragraph 0026 teaches that the ultrasound can within a range of frequencies. Paragraph 0103 teaches consideration of the frequency),
wherein the patient interface is configured to acoustically couple the plurality of ultrasound transducers to the skin surface of the head (Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain. Paragraph 0119 teaches that each individual signal of the transducers is determined and obtained for the purpose of ensuring accurate focusing).
However, Aubry is silent regarding a method, comprising
providing a non-invasive sonodynamic therapy system configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells;
modulating a duty-cycle of the signal to generate ultrasonic acoustic waves having an acoustic intensity.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method, comprising:
providing a non-invasive sonodynamic therapy system configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells (Abstract teaches that the invention uses the ultrasound along with chemical agents to perform SDT. The Fig. 5 shows the patient interface where the head portion also has the ultrasound transducers 52. Paragraph 0032 teaches that the SDT is able to treat cancer. Fig. 1-4 shows the system interacting with the patient),
wherein the non-invasive sonodynamic therapy system comprises:
a patient interface (The Fig. 5 shows the patient interface where the head portion also has the ultrasound transducers 52);
a plurality of ultrasound transducers wherein each of ultrasound transducers of the plurality of ultrasound transducers is configured to emit a focused acoustic waves through the skull (Paragraph 0038 teaches that the ultrasound used in the SDT can be focused ultrasound. The Fig. 5 shows the patient interface where the head portion also has the ultrasound transducers 52).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of ultrasound treatment for non-invasive SDT. Galkin teaches that the implementation of sonodynamic treatment can be done for neurological conditions and disorders (Pages 99-106 of Galkin). This treatment supplements existing surgical and radiation treatments for CND diseases. Furthermore, this modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
However, Chen is silent regarding a method, comprising:
modulating a duty-cycle of the signal to generate ultrasonic acoustic waves having an acoustic intensity.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, comprising:
modulating a duty-cycle of the signal to generate ultrasonic acoustic waves having an acoustic intensity (Paragraphs 0112, 0114, 0123, 0125, 0158, 0160, 0162, 0213 teaches a duty cycle of 50% and a power density of 3Wcm-2. Paragraph 0221 teaches a duty cycle of 30% and a power density of 3.5Wcm-2 which is the spatial average temporal peak. Paragraph 0092 teaches of the ultrasound may range from about 0.1 Wcm-2 to about 1 kWcm-2, preferably from about 1 to about 50 Wcm-2).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Chen with Callan’s teaching of a duty cycle and acoustic intensity. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Regarding claim 8, modified Aubry teaches the method in claim 7, as discussed above.
Aubry further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell (Paragraph 0080 teaches that the cup 11 is rigid. Cup 11 in Fig. 2. Paragraph 0080 teaches that the cap 2 has a flexible wall 12 that holds a liquid. Wall 12 in Fig. 2. Paragraph 0078 teaches that the cap 2 is controlled by a robotic arm 4. See Fig. 1).
Regarding claim 9, modified Aubry teaches the method in claim 7, as discussed above.
However, the combination of Aubry and Chen is silent regarding a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Paragraph 0118 teaches the insertion and monitoring of the fluorescence 30 min after the intravenous administration. Paragraph 0173 teaches the ultrasound application for about 3 min after IV administration. Paragraph 0092 teaches transmission from 1 ms to 20 min).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Chen with Callan’s teaching of therapy for 30 min to an hour. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Regarding claim 10, modified Aubry teaches the method in claim 7, as discussed above.
Aubry further teaches a method, wherein the signal is a pulse signal to pulse the focused acoustic waves to affect a spatial variation of the acoustic intensity in the brain at the tumor cells of the patient (Paragraph 0073 teaches that tumors can be treated. Figs. 1-2 show the treatment of the patient head. Paragraph 0077 teaches that the ultrasound waves can be forces in the patient head. Paragraph 0109 teaches the propagation of the waves at the points 18. Paragraph 0121 teaches that the spatial and time variation can be performed).
Alternatively, in an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method, wherein the signal is a pulse signal to pulse the focused acoustic waves to affect a spatial variation of the acoustic intensity in the brain at the tumor cells of the patient (Paragraph 0032 teaches that the SDT is used to target sonosensitizer compounds to treat cancers with ultrasonic intensity to activate the cytotoxicity. Fig. 5 shows the concentric flat ultrasound transducers that target patient head. Paragraph 0081 teaches that the patient head can be targeted. Paragraph 0038 teaches focused ultrasound is used in SDT to target a specific area and protect surrounding non-diseased tissue from activated sonosensitizers).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of minimizing spatial variation of acoustic intensity in target areas. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
Regarding claim 11, modified Aubry teaches the method in claim 7, as discussed above.
While Aubry teaches frequency in a range of 20 kHz to 2 MHz to the tumor cells in the brain (Paragraphs 0026 and 0073), Aubry is silent regarding a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer (Paragraph 0092 teaches that the ultrasound is at frequencies greater than 20 kHz, and preferably in the range from 200 kHz to 3 MHz for applications that penetrate deep into the body. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
Regarding claim 13, Aubry teaches a method of non-invasive ultrasound, comprising:
providing a patient interface configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises at least one array of ultrasound transducer elements (Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Fig. 2 shows the rigid cup 11 holding the transducer array 17. Paragraph 0080 teaches the transducers are on the cup 11. Paragraph 0080 teaches that the wall 12 holds a liquid like water. Paragraph 0072 teaches that the system is able to perform hyperthermia treatment. The liquid is used to keep the patient from overheating in such hyperthermia treatments. See Fig. 2);
wherein each ultrasound transducer elements of the at least one array of ultrasound transducer elements is configured to emit a focused acoustic waves through the skull (Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain. Paragraph 0119 teaches that each individual signal of the transducers is determined and obtained for the purpose of ensuring accurate focusing. Paragraph 0079 teaches that the microcomputer controls the transducer arrays. Paragraph 0115 teaches that the ultrasound waves can be focused to targets in the brain. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Paragraph 0026 teaches that the ultrasound can within a range of frequencies. Paragraph 0103 teaches consideration of the frequency);
driving the at least one array of ultrasound transducer elements with a signal (Paragraph 0079 teaches that the microcomputer controls the transducer arrays),
wherein the signal is configured to deliver the acoustic intensity in the brain at the tumor cells of the patient (Paragraph 0115 teaches that the ultrasound waves can be focused to targets in the brain. Paragraph 0073 teaches that the ultrasound transmission can be done for the treatment of tumors. Paragraph 0026 teaches that the ultrasound can within a range of frequencies).
However, Aubry is silent regarding a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer;
modulating a duty-cycle of the signal to cause the focused acoustic waves to have an acoustic intensity with modulated duty cycle.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer (Abstract teaches that the invention uses the ultrasound along with chemical agents to perform SDT. The Fig. 5 shows the patient interface where the head portion also has the ultrasound transducers 52. Paragraph 0032 teaches that the SDT is able to treat cancer. Fig. 1-4 shows the system interacting with the patient. Paragraph 0038 teaches that the ultrasound used in the SDT can be focused ultrasound).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of performing SDT. Galkin teaches that the implementation of sonodynamic treatment can be done for neurological conditions and disorders (Pages 99-106 of Galkin). This treatment supplements existing surgical and radiation treatments for CND diseases. Furthermore, this modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
However, Chen is silent regarding a method, comprising:
modulating a duty-cycle of the signal to cause the focused acoustic waves to have an acoustic intensity with modulated duty cycle.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, comprising:
modulating a duty-cycle of the signal to cause the focused acoustic waves to have an acoustic intensity with modulated duty cycle (Paragraphs 0112, 0114, 0123, 0125, 0158, 0160, 0162, 0213 teaches a duty cycle of 50% and a power density of 3Wcm-2. Paragraph 0221 teaches a duty cycle of 30% and a power density of 3.5Wcm-2 which is the spatial average temporal peak. Paragraph 0092 teaches of the ultrasound may range from about 0.1 Wcm-2 to about 1 kWcm-2, preferably from about 1 to about 50 Wcm-2).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Chen with Callan’s teaching of a duty cycle and acoustic intensity. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Regarding claim 14, modified Aubry teaches the method in claim 13, as discussed above.
Aubry further teaches a method, wherein the focused acoustic waves comprise a frequency of 1 MHz (Paragraph 0026 teaches that the frequency of the ultrasound can be at in the range of 0.5-3 MHZ).
Regarding claim 15, modified Aubry teaches the method in claim 13, as discussed above.
Aubry further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell (Paragraph 0080 teaches that the cup 11 is rigid. Cup 11 in Fig. 2. Paragraph 0080 teaches that the cap 2 has a flexible wall 12 that holds a liquid. Wall 12 in Fig. 2. Paragraph 0078 teaches that the cap 2 is controlled by a robotic arm 4. See Fig. 1).
Regarding claim 16, modified Aubry teaches the method in claim 13, as discussed above.
However, the combination of Aubry and Chen is silent regarding a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Paragraph 0118 teaches the insertion and monitoring of the fluorescence 30 min after the intravenous administration. Paragraph 0173 teaches the ultrasound application for about 3 min after IV administration. Paragraph 0092 teaches transmission from 1 ms to 20 min).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Chen with Callan’s teaching of therapy for 30 min to an hour. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Regarding claim 17, modified Aubry teaches the method in claim 13, as discussed above.
Aubry further teaches a method, wherein the focused acoustic waves comprise a frequency in a range of 20 kHz to 2 MHz (Paragraph 0026 teaches that the ultrasound frequencies is in the range of 0.5-3 MHz. Paragraph 0119 teaches that the ultrasound transmission is focused).
However, Aubry is silent regarding a method, wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves, the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the focused acoustic waves comprise a frequency in a range of 20 kHz to 2 MHz (Paragraph 0092 teaches that the ultrasound is at frequencies greater than 20 kHz, and preferably in the range from 200 kHz to 3 MHz for applications that penetrate deep into the body. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves, the sonosensitizer is a porphyrin compound (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
Regarding claim 18, modified Aubry teaches the method in claim 14, as discussed above.
However, Aubry is silent regarding a method, further comprising administering microbubbles to the tumor cells,
wherein the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
However, Chen is silent regarding a method, further comprising administering microbubbles to the tumor cells.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, further comprising administering microbubbles to the tumor cells (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Chen with Callan’s teaching of administering microbubbles to tumors. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Claims 12 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Aubry et al. (PGPUB No. US 2005/0277824) in view of Chen (PGPUB No. US 2009/0062724) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Liu (PGPUB No. US 2018/0207447).
Regarding claim 12, modified Aubry teaches the method in claim 7, as discussed above.
While Aubry and Chen teach tumor treatment with ultrasound (Paragraph 0073 of Aubry and paragraph 0032 of Chen), the combination of Aubry, Chen, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry, Chen, and Callan with Liu’s teaching of the use of ALA for GBM treatment via SDT. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Regarding claim 20, modified Aubry teaches the method in claim 13, as discussed above.
However, Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
However, the combination of Aubry and Chen is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry and Chen with Callan’s teaching of the use of protoporphyrin for SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
However, the combination of Aubry, Chen, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry, Chen, and Callan with Liu’s teaching of treating GBM with ALA and PpIX to produce ROS for apoptosis. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Aubry et al. (PGPUB No. US 2005/0277824) in view of Chen (PGPUB No. US 2009/0062724) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Hynynen et al. (PGPUB No. US 2018/0177491).
Regarding claim 19, modified Aubry teaches the method in claim 13, as discussed above.
However, Aubry is silent regarding a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse; and
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT),
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
However, the combination of Aubry, Chen, and Callan is silent regarding a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Hynynen teaches a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse (Fig. 14 shows sinusoidal ultrasound transmission. Fig. 17 shows sinusoidal signal with repeating peaks).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Aubry, Chen, and Callan with Hynynen’s teaching of data transmission sets with sine waves. This modified method would allow for a user to have better focusing and steering range (Paragraph 0131 of Hynynen). Furthermore, the modified method would allow for less variability and improved correction of wave propagation (Paragraph 0131 of Hynynen).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 8 of U.S. Patent No. 11,730,980 in view of Aubry et al. (PGPUB No. US 2005/0277824).
Regarding claim 1, Claim 1 of U.S. Patent No. 11,730,980 teaches method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a patient interface configured for coupling to a skin surface of a head of a patient with a brain with tumor cells, the patient interface comprising an ultrasound transducer array and a cooling system, the cooling system comprising one or more cooling channels comprising independent loops forming a manifold around the skull, the manifold connecting an inlet tube and an outlet tube; and generating a signal to actuate the ultrasound transducer array; wherein the ultrasound transducer array comprises a plurality of ultrasound transducer elements, wherein the ultrasound transducer array is configured to emit acoustic waves having an acoustic intensity, wherein at least one of ultrasound transducers of the ultrasound transducer array is configured to emit a focused acoustic wave through the skull, wherein the patient interface is configured to acoustically couple the ultrasound transducer array to the skin surface, wherein the patient interface is configured for conforming to the skin surface, wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies to deliver the focused acoustic waves in the brain at the tumor cells of the patient; and circulating a fluid through the one or more cooling channels to reduce heat at the head of the patient at the patient interface (Claim 1 recites: A method of using planar acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a head of a patient with a brain with tumor cells, the patient interface comprising: a flexible membrane, a rigid shell, and a cooling system, wherein the flexible membrane is couplable to the rigid shell, wherein the rigid shell comprises an array of flat piezoelectric transducers, wherein each of the flat piezoelectric transducers is configured to emit a planar acoustic wave through a bone of the skull, wherein the patient interface is configured to acoustically couple the array of flat piezoelectric transducers to the skin surface, wherein the flexible membrane is configured for conforming to the skin surface: driving the array of flat piezoelectric transducers with a signal, wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the brain with the tumor cells of the patient, wherein the signal is consistently frequency modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different frequencies in a range of 898 kHz to 1.107 MHz to modulate the planar acoustic wave to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain, wherein the signal is further consistently duty cycle modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different duty cycles thereby minimizing the spatial variation of the acoustic intensity in the brain at the tumor cells of the patient; and circulating a fluid through cooling channels in the cooling system to reduce heat at the head of the patient at the patient interface, wherein the cooling channels comprise independent loops connected to an inlet tube and an outlet tube via a manifold, wherein the fluid is configured to acoustically couple the array of flat piezoelectric transducers to the flexible membrane).
However, the claims of U.S. Patent No. 11,730,980 is silent regarding a method, using focused acoustic waves.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain. Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain. Paragraph 0119 teaches that each individual signal of the transducers is determined and obtained for the purpose of ensuring accurate focusing. Paragraph 0086 teaches the use of the sub-arrays for the individualized emission).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 2, modified U.S. Patent No. 11,730,980 teaches the method in claim 1, as discussed above.
Claim 5 of U.S. Patent No. 11,730,980 further teaches a method, further comprising moving the patient interface with respect to the head of the patient (Claim 5 recites “wherein the rigid shell is connected to a mobile stand, and further comprising moving the rigid shell with respect to the patient via the mobile stand”).
Regarding claim 3, modified U.S. Patent No. 11,730,980 teaches the method in claim 1, as discussed above.
Claim 1 of U.S. Patent No. 11,730,980 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell, and a flexible shell (Claim 1 recites “the patient interface comprising: a flexible membrane, a rigid shell, and a cooling system”).
Claims 4 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 8 of U.S. Patent No. 11,730,980 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872
Regarding claim 4, modified U.S. Patent No. 11,730,980 teaches the method in claim 1, as discussed above.
However, the combination of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Paragraph 0118 teaches the insertion and monitoring of the fluorescence 30 min after the intravenous administration. Paragraph 0173 teaches the ultrasound application for about 3 min after IV administration. Paragraph 0092 teaches transmission from 1 ms to 20 min).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of U.S. Patent No. 11,730,980 and Aubry with Callan’s teaching of therapy for 30 min to an hour. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Claim 5-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, and 8 of U.S. Patent No. 11,730,980 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Liu (PGPUB No. US 2018/0207447).
Regarding claim 5, modified U.S. Patent No. 11,730,980 teaches the method in claim 1, as discussed above.
However, the combination of the claims of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method,
wherein the sonosensitizer is a porphyrin compound (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS),
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of U.S. Patent No. 11,730,980 and Aubry with Callan’s teaching of the use of protoporphyrin for SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
However, the combination of U.S. Patent No. 11,730,980, Aubry, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of U.S. Patent No. 11,730,980, Aubry, and Callan with Liu’s teaching of the administration of ALA and the treatment of GBM. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Regarding claim 6, modified U.S. Patent No. 11,730,980 teaches the method in claim 1, as discussed above.
Claim 8 of U.S. Patent No. 11,730,980 further teaches a method, wherein the ultrasound transducer array comprises a grid of elements (Col. 8, lines 10-18, recite “wherein the array of flat piezoelectric transducers comprises a grid of concentric elements, wherein the acoustic intensity is in a range of 0.2 W/cm.sup.2 to 20 W/cm.sup.2 to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX”.),
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves (Col. 8, lines 10-18, recite “wherein the array of flat piezoelectric transducers comprises a grid of concentric elements, wherein the acoustic intensity is in a range of 0.2 W/cm.sup.2 to 20 W/cm.sup.2 to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX”.),
wherein the average acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2 to activate the sonosensitizer (Col. 8, lines 10-18, recite “wherein the array of flat piezoelectric transducers comprises a grid of concentric elements, wherein the acoustic intensity is in a range of 0.2 W/cm.sup.2 to 20 W/cm.sup.2 to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX”).
However, the combination of the claims of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the sonosensitizer is a porphyrin compound (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers),
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site),
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2 to activate the sonosensitizer (Paragraph 0092 teaches of the ultrasound may range from about 0.1 Wcm-2 to about 1 kWcm-2, preferably from about 1 to about 50 Wcm-2).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of the claims of U.S. Patent No. 11,730,980 and Aubry with Callan’s teaching of the use of protoporphyrin for SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
However, the combination of U.S. Patent No. 11,730,980, Aubry, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the sonosensitizer is a porphyrin compound (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of the claims of U.S. Patent No. 11,730,980, Aubry, and Callan with Liu’s teaching of SDT treatment with ALA and a specific acoustic energy. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claims 7-8, 10, 13-15, and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 9-10 of U.S. Patent No. 11,730,980 in view of Aubry et al. (PGPUB No. US 2005/0277824).
Regarding claim 7, claim 9 of U.S. Patent No. 11,730,980 teaches a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a non-invasive sonodynamic therapy system configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells, wherein the non-invasive sonodynamic therapy system comprises: a patient interface, and a plurality of ultrasound transducers wherein each of ultrasound transducers of the plurality of ultrasound transducers is configured to emit a focused acoustic wave through the skull; driving the plurality of ultrasound transducers with a signal, modulating a duty-cycle of the signal to generate ultrasonic acoustic waves having an acoustic intensity; wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies with the acoustic intensity in the brain at the tumor cells of the patient, wherein the patient interface is configured to acoustically couple the plurality of ultrasound transducers to the skin surface of the head (Claim 9 recites: A method of using planar acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a non-invasive sonodynamic therapy system to a skin surface of a head of a patient with a brain with tumor cells, wherein the non-invasive sonodynamic therapy system comprises: a patient interface, a cooling system, a rigid shell, and an array of flat piezoelectric transducers wherein each of the flat piezoelectric transducers is configured to emit a planar acoustic wave through a bone of the skull; driving the array of flat piezoelectric transducers with a signal, wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the brain with the tumor cells of the patient, wherein the signal is consistently frequency modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different frequencies to modulate the planar acoustic wave to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain, wherein the signal is frequency modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with the variety of different frequencies thereby minimizing the spatial variation of the acoustic intensity in the brain at the tumor c ells of the patient, wherein the signal is further consistently duty cycle modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different duty cycles thereby minimizing the spatial variation of the acoustic intensity in the brain at the tumor cells of the patient, wherein the patient interface is configured to acoustically couple the array of flat piezoelectric transducers to the skin surface of the head with a flexible membrane; and circulating a fluid through cooling channels in the cooling system to reduce heat at the skin surface of the head of the patient, wherein the cooling channels comprise independent loops connected to an inlet tube and an outlet tube via a manifold, wherein the fluid is configured to acoustically couple to the array of flat piezoelectric transducers to the flexible membrane).
However, the claims of U.S. Patent No. 11,730,980 are silent regarding a method, using focused acoustic waves.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain. Fig. 2 shows the cap 2 is holding the transducer array 17 and is worn by the patient P. Also see Fig. 1. Paragraph 0082 teaches that the transducer array 17 is used for ultrasound transmission with respect to the patient. Abstract teaches that the transducers are transmitted ultrasound waves into the skull and brain. Paragraph 0119 teaches that each individual signal of the transducers is determined and obtained for the purpose of ensuring accurate focusing. Paragraph 0086 teaches the use of the sub-arrays for the individualized emission).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 8, modified U.S. Patent No. 11,730,980 teaches the method in claim 7, as discussed above.
Claim 9 of U.S. Patent No. 11,730,980 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell (Claim 9 recites “wherein the non-invasive sonodynamic therapy system comprises: a patient interface, a cooling system, a rigid shell, and an array of flat piezoelectric transducers wherein each of the flat piezoelectric transducers is configured to emit a planar acoustic wave through a bone of the skull”).
Regarding claim 10, modified U.S. Patent No. 11,730,980 teaches the method in claim 7, as discussed above.
Claim 10 of U.S. Patent No. 11,730,980 further teaches a method, wherein the signal is a pulse signal to pulse the focused acoustic waves to affect a spatial variation of the acoustic intensity in the brain at the tumor cells of the patient (Claim 10 recites “wherein the signal is further consistently duty cycle modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different duty cycles thereby minimizing the spatial variation of the acoustic intensity in the brain at the tumor cells of the patient”).
However, the claims of U.S. Patent No. 11,730,980 are silent regarding a method, using focused acoustic waves.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 13, claim 1 of U.S. Patent No. 11,730,980 teaches a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a patient interface configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises at least one array of ultrasound transducer elements, wherein each ultrasound transducer elements of the at least one array of ultrasound transducer elements is configured to emit a focused acoustic waves through the skull; driving the at least one array of ultrasound transducer elements with a signal, modulating a duty-cycle of the signal to cause the focused acoustic waves to have an acoustic intensity with modulated duty cycle; wherein the signal is configured to deliver the acoustic intensity in the brain at the tumor cells of the patient (Claim 1 recites: A method of using planar acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a head of a patient with a brain with tumor cells, the patient interface comprising: a flexible membrane, a rigid shell, and a cooling system, wherein the flexible membrane is couplable to the rigid shell, wherein the rigid shell comprises an array of flat piezoelectric transducers, wherein each of the flat piezoelectric transducers is configured to emit a planar acoustic wave through a bone of the skull, wherein the patient interface is configured to acoustically couple the array of flat piezoelectric transducers to the skin surface, wherein the flexible membrane is configured for conforming to the skin surface: driving the array of flat piezoelectric transducers with a signal, wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the brain with the tumor cells of the patient, wherein the signal is consistently frequency modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different frequencies in a range of 898 kHz to 1.107 MHz to modulate the planar acoustic wave to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain, wherein the signal is further consistently duty cycle modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different duty cycles thereby minimizing the spatial variation of the acoustic intensity in the brain at the tumor cells of the patient; and circulating a fluid through cooling channels in the cooling system to reduce heat at the head of the patient at the patient interface, wherein the cooling channels comprise independent loops connected to an inlet tube and an outlet tube via a manifold, wherein the fluid is configured to acoustically couple the array of flat piezoelectric transducers to the flexible membrane).
However, the claims of U.S. Patent No. 11,730,980 are silent regarding a method, using focused acoustic waves.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 14, modified U.S. Patent No. 11,730,980 teaches the method in claim 13, as discussed above.
Claim 1 of U.S. Patent No. 11,730,980 further teaches a method, wherein the focused acoustic waves comprise a frequency of 1 MHz (Claim 1 recite “wherein the signal is consistently frequency modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different frequencies in a range of 898 kHz to 1.107 MHz to modulate the planar acoustic wave to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain”).
Regarding claim 15, modified U.S. Patent No. 11,730,980 teaches the method in claim 13, as discussed above.
Claim 1 of U.S. Patent No. 11,730,980 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell (Claim 1 recites “the patient interface comprising: a flexible membrane, a rigid shell, and a cooling system”).
Regarding claim 17, modified U.S. Patent No. 11,730,980 teaches the method in claim 13, as discussed above.
Claim 7 of U.S. Patent No. 11,730,980 further teaches a method, wherein the acoustic waves comprise a frequency in a range of 20 kHz to 2 MHz (Claim 1 recites “Claim 1 recite “wherein the signal is consistently frequency modulated to drive each of the flat piezoelectric transducers of the array of flat piezoelectric transducers with a variety of different frequencies in a range of 898 kHz to 1.107 MHz to modulate the planar acoustic wave to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain””),
wherein the sonosensitizer becomes cytotoxic upon exposure to the acoustic waves (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”),
wherein the sonosensitizer is a porphyrin compound (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”).
However, the claims of U.S. Patent No. 11,730,980 are silent regarding a method, using focused acoustic waves.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 18, modified U.S. Patent No. 11,730,980 teaches the method in claim 14, as discussed above.
Claim 7 of U.S. Patent No. 11,730,980 further teaches a method, wherein comprising administering microbubbles to the tumor cells,
wherein the sonosensitizer is a porphyrin compound (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”).
Claims 9, 11, and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 7, and 9-10 of U.S. Patent No. 11,730,980 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872).
Regarding claim 9, modified U.S. Patent No. 11,730,980 teaches the method in claim 7, as discussed above.
However, the combination of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Paragraph 0118 teaches the insertion and monitoring of the fluorescence 30 min after the intravenous administration. Paragraph 0173 teaches the ultrasound application for about 3 min after IV administration. Paragraph 0092 teaches transmission from 1 ms to 20 min).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of U.S. Patent No. 11,730,980 and Aubry with Callan’s teaching of therapy for 30 min to an hour. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Regarding claim 11, modified U.S. Patent No. 11,730,980 teaches the method in claim 7, as discussed above.
However, the combination of the claims of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer (Paragraph 0092 teaches frequencies will typically be in the range 20 kHz to 10 MHz, preferably 0.1 to 2 MHz for the destruction of the microbubble. Abstract teaches sonodynamic therapy. Paragraph 005 teaches ultrasound focus),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS),
wherein the sonosensitizer is a porphyrin compound (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of the claims of U.S. Patent No. 11,730,980 and Aubry with Callan’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Regarding claim 16, modified U.S. Patent No. 11,730,980 teaches the method in claim 13, as discussed above.
However, the combination of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Paragraph 0118 teaches the insertion and monitoring of the fluorescence 30 min after the intravenous administration. Paragraph 0173 teaches the ultrasound application for about 3 min after IV administration. Paragraph 0092 teaches transmission from 1 ms to 20 min).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of U.S. Patent No. 11,730,980 and Aubry with Callan’s teaching of therapy for 30 min to an hour. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Claims 12 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 9-10 are of U.S. Patent No. 11,730,980 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Liu (PGPUB No. US 2018/0207447).
Regarding claim 12, modified U.S. Patent No. 11,730,980 teaches the method in claim 7, as discussed above.
However, the combination of the claims of U.S. Patent No. 11,730,980, Aubry, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of the claims of U.S. Patent No. 11,730,980, Aubry, and Callan with Liu’s teaching of SDT treatment with ALA and a specific acoustic energy. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Regarding claim 20, modified U.S. Patent No. 11,730,980 teaches the method in claim 13, as discussed above.
Claim 7 of U.S. Patent No. 11,730,980 further teaches a method, wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”),
wherein the sonosensitizer is a porphyrin compound (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”),
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”).
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
However, the combination of the claims of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of the claims of U.S. Patent No. 11,730,980 and Aubry with Liu’s teaching of treating GBM with ALA and PpIX to produce ROS for apoptosis. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 9-10 of U.S. Patent No. 11,730,980 in view of Aubry et al. (PGPUB No. US 2005/0277824) in view of Hynynen et al. (PGPUB No. US 2018/0177491).
Regarding claim 19, modified U.S. Patent No. 11,730,980 teaches the method in claim 13, as discussed above.
Claim 7 of U.S. Patent No. 11,730,980 further teaches a method, wherein the sonosensitizer is a porphyrin compound (Claim 7 recites “wherein the frequency modulated signal is configured to activate the sonosensitizer, wherein the sonosensitizer is a drug that becomes cytotoxic upon exposure to the planar acoustic wave, wherein the sonosensitizer is protoporphyrin IX, wherein the signal is configured to activate the protoporphyrin IX to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells”).
However, the combination of the claims of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Hynynen teaches a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse (Fig. 14 shows sinusoidal ultrasound transmission. Fig. 17 shows sinusoidal signal with repeating peaks).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of the claims of U.S. Patent No. 11,730,980 and Aubry with Hynynen’s teaching of data transmission sets with sine waves. This modified method would allow for a user to have better focusing and steering range (Paragraph 0131 of Hynynen). Furthermore, the modified method would allow for less variability and improved correction of wave propagation (Paragraph 0131 of Hynynen).
Claims 1-4 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 7-8 of U.S. Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824).
Regarding claim 1, Claim 1 of U.S. Patent No. 11,975,156 teaches method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a patient interface configured for coupling to a skin surface of a head of a patient with a brain with tumor cells, the patient interface comprising an ultrasound transducer array and a cooling system, the cooling system comprising one or more cooling channels comprising independent loops forming a manifold around the skull, the manifold connecting an inlet tube and an outlet tube; and generating a signal to actuate the ultrasound transducer array; wherein the ultrasound transducer array comprises a plurality of ultrasound transducer elements, wherein the ultrasound transducer array is configured to emit acoustic waves having an acoustic intensity, wherein at least one of ultrasound transducers of the ultrasound transducer array is configured to emit a focused acoustic wave through the skull, wherein the patient interface is configured to acoustically couple the ultrasound transducer array to the skin surface, wherein the patient interface is configured for conforming to the skin surface, wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies to deliver the focused acoustic waves in the brain at the tumor cells of the patient; and circulating a fluid through the one or more cooling channels to reduce heat at the head of the patient at the patient interface (Claim 1 recites: A method of using planar or defocused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises an array of piezoelectric transducers and a cooling system, wherein each of the piezoelectric transducers is configured to emit acoustic waves through the skull, wherein the acoustic waves are planar or defocused; wherein the patient interface is configured to acoustically couple the array of piezoelectric transducers to the skin surface of the head of the patient, driving the array of piezoelectric transducers with a signal, wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the brain with the tumor cells of the patient, wherein the signal is consistently frequency modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with one or more frequencies to modulate the acoustic waves to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain, wherein the signal is further consistently duty cycle modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with a variety of different duty cycles thereby minimizing the spatial variation of the acoustic intensity at the tumor cells of the patient; and circulating a fluid through cooling channels in the cooling system to reduce heat at the patient interface, wherein the cooling channels comprise independent loops connected to an inlet tube and an outlet tube via a manifold).
However, the claims of US Patent No. 11,975,156 is silent regarding a method, using focused acoustic waves.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify US Patent No. 11,975,156 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 2, modified U.S. Patent No. 11,975,156 teaches the method in claim 1, as discussed above.
Claim 5 of U.S. Patent No. 11,975,156 further teaches a method, further comprising moving the patient interface with respect to the head of the patient (Claim 5 recites “wherein the patient interface is connected to a stand, and further comprising moving the patient interface with respect to the patient via the stand”).
Regarding claim 3, modified U.S. Patent No. 11,975,156 teaches the method in claim 1, as discussed above.
Claim 8 of U.S. Patent No. 11,975,156 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell, and a flexible shell (Claim 8 recites “wherein the patient interface comprises at least one of a cap, a rigid shell or a flexible shell”).
Regarding claim 4, modified U.S. Patent No. 11,975,156 teaches the method in claim 1, as discussed above.
Claim 7 of U.S. Patent No. 11,975,156 further teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Claim 7 recites “wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour”).
Claim 5 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 7-8 of U.S. Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Liu (PGPUB No. US 2018/0207447).
Regarding claim 5, modified U.S. Patent No. 11,975,156 teaches the method in claim 1, as discussed above.
However, the claims of U.S. Patent No. 11,975,156 is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,975,156 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method,
wherein the sonosensitizer is a porphyrin compound (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS),
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of U.S. Patent No. 11,975,156 and Aubry with Callan’s teaching of the use of protoporphyrin for SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
However, the combination of U.S. Patent No. 11,975,156, Aubry, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of U.S. Patent No. 11,975,156, Aubry, and Callan with Liu’s teaching of the administration of ALA and the treatment of GBM. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claim 6 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 5, 7-8 of U.S. Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Chen (PGPUB No. US 2009/0062724) further in view of Liu (PGPUB No. US 2018/0207447).
Regarding claim 6, modified US Patent No. 11,975,156 teaches the method in claim 1, as discussed above.
However, the claims of U.S. Patent No. 11,730,980 is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the ultrasound transducer array comprises a grid of elements, wherein the sonosensitizer is a porphyrin compound,
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2to activate the sonosensitizer.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify US Patent No. 11,975,156 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the ultrasound transducer array comprises a grid of elements (Fig. 5 shows a grid of concentric flat ultrasound elements), wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT),
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156, Aubry, and Callan with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
However, Chen is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2to activate the sonosensitizer.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the sonosensitizer is a porphyrin compound (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT),
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2 to activate the sonosensitizer (Paragraph 0053 teaches that the ultrasound power is at 0.4 1 W/cm2 for the SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156, Aubry, Callan, and Chen with Liu’s teaching of SDT treatment with ALA and a specific acoustic energy. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claims 7-10 and 13-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9, and 13 of U.S. Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824).
Regarding claim 7, Claim 1 of U.S. Patent No. 11,975,156 teaches a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a non-invasive sonodynamic therapy system configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells, wherein the non-invasive sonodynamic therapy system comprises: a patient interface, and a plurality of ultrasound transducers wherein each of ultrasound transducers of the plurality of ultrasound transducers is configured to emit a focused acoustic wave through the skull; driving the plurality of ultrasound transducers with a signal, modulating a duty-cycle of the signal to generate ultrasonic acoustic waves having an acoustic intensity; wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies with the acoustic intensity in the brain at the tumor cells of the patient, wherein the patient interface is configured to acoustically couple the plurality of ultrasound transducers to the skin surface of the head (Claim 1 recites: A method of using planar or defocused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises an array of piezoelectric transducers and a cooling system, wherein each of the piezoelectric transducers is configured to emit acoustic waves through the skull, wherein the acoustic waves are planar or defocused; wherein the patient interface is configured to acoustically couple the array of piezoelectric transducers to the skin surface of the head of the patient, driving the array of piezoelectric transducers with a signal, wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the brain with the tumor cells of the patient, wherein the signal is consistently frequency modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with one or more frequencies to modulate the acoustic waves to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain, wherein the signal is further consistently duty cycle modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with a variety of different duty cycles thereby minimizing the spatial variation of the acoustic intensity at the tumor cells of the patient; and circulating a fluid through cooling channels in the cooling system to reduce heat at the patient interface, wherein the cooling channels comprise independent loops connected to an inlet tube and an outlet tube via a manifold).
However, the claims of US Patent No. 11,975,156 is silent regarding a method, using focused acoustic waves.
It an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify US Patent No. 11,975,156 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 8, modified US Patent No. 11,975,156 teaches the method in claim 7, as discussed above.
Claim 8 of US Patent No. 11,975,156 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell (Claim 8 recites “wherein the patient interface comprises at least one of a cap, a rigid shell or a flexible shell”).
Regarding claim 9, modified US Patent No. 11,975,156 teaches the method in claim 7, as discussed above.
Claim 7 of US Patent No. 11,975,156 further teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Claim 7 recites “wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour”).
Regarding claim 10, modified US Patent No. 11,975,156 teaches the method in claim 7, as discussed above.
Claim 13 of US Patent No. 11,975,156 further teaches a method, wherein the signal is a pulse signal to pulse the focused acoustic waves to affect a spatial variation of the acoustic intensity in the brain at the tumor cells of the patient (Claim 13 recites “wherein the signal is a pulse signal configured to pulse the acoustic waves thereby minimizing the spatial variation of the acoustic intensity in the brain at the tumor cells of the patient.”).
Regarding claim 13, Claim 1 of U.S. Patent No. 11,975,156 teaches a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a patient interface configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises at least one array of ultrasound transducer elements, wherein each ultrasound transducer elements of the at least one array of ultrasound transducer elements is configured to emit a focused acoustic waves through the skull; driving the at least one array of ultrasound transducer elements with a signal, modulating a duty-cycle of the signal to cause the focused acoustic waves to have an acoustic intensity with modulated duty cycle; wherein the signal is configured to deliver the acoustic intensity in the brain at the tumor cells of the patient (Claim 1 recites: A method of using planar or defocused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises an array of piezoelectric transducers and a cooling system, wherein each of the piezoelectric transducers is configured to emit acoustic waves through the skull, wherein the acoustic waves are planar or defocused; wherein the patient interface is configured to acoustically couple the array of piezoelectric transducers to the skin surface of the head of the patient, driving the array of piezoelectric transducers with a signal, wherein the signal is configured to minimize a spatial variation of an acoustic intensity in the brain with the tumor cells of the patient, wherein the signal is consistently frequency modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with one or more frequencies to modulate the acoustic waves to produce the acoustic intensity at the sonosensitizer in a treatment region to treat the tumor cells in the brain, wherein the signal is further consistently duty cycle modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with a variety of different duty cycles thereby minimizing the spatial variation of the acoustic intensity at the tumor cells of the patient; and circulating a fluid through cooling channels in the cooling system to reduce heat at the patient interface, wherein the cooling channels comprise independent loops connected to an inlet tube and an outlet tube via a manifold).
However, the claims of US Patent No. 11,975,156 is silent regarding a method, using focused acoustic waves.
It an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify US Patent No. 11,975,156 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 14, modified US Patent No. 11,975,156 teaches the method in claim 13, as discussed above.
Claim 9 of US Patent No. 11,975,156 further teaches a method, wherein the focused acoustic waves comprise a frequency of 1 MHz (Col. 29, lines 49-51 recites “wherein the one or more frequencies comprises a range between 898 kHz and 1.107 MHz”).
Regarding claim 15, modified US Patent No. 11,975,156 teaches the method in claim 13, as discussed above.
Claim 8 of US Patent No. 11,975,156 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell (Col. 29, lines 46-48 recites “wherein the patient interface comprises at least one of a cap, a rigid shell or a flexible shell”).
Regarding claim 16, modified US Patent No. 11,975,156 teaches the method in claim 13, as discussed above.
Claim 7 of US Patent No. 11,975,156 further teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Col. 29, lines 44-45 recites “wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour”).
Claim 11 and 17 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9, and 13 of U.S. Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Chen (PGPUB No. US 2009/0062724).
Regarding claim 11, modified U.S. Patent No. 11,730,980 teaches the method in claim 7, as discussed above.
However, the combination of the claims of U.S. Patent No. 11,730,980 and Aubry is silent regarding a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify U.S. Patent No. 11,730,980 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer (Paragraph 0092 teaches that the ultrasound is at frequencies greater than 20 kHz, and preferably in the range from 200 kHz to 3 MHz for applications that penetrate deep into the body. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156 and Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-borne cancers (Paragraphs 0037-0038 of Chen).
Regarding claim 17, modified US Patent No. 11,975,156 teaches the method in claim 13, as discussed above.
Claim 12 of US Patent No. 11,975,156 further teaches a method, wherein the focused acoustic waves comprise a frequency in a range of 20 kHz to 2 MHz (Col. 29, lines 61-65 recites “wherein the one or more frequencies comprises a frequency in a range of 650 kHz to 2 MHz thereby minimizing the spatial variation of the acoustic intensity in the brain at the tumor cells of the patient”).
However, the combination of the claims of US Patent No. 11,975,156 and Aubry is silent regarding a method, wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves, the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify US Patent No. 11,975,156 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the focused acoustic waves comprise a frequency in a range of 20 kHz to 2 MHz (Paragraph 0092 teaches that the ultrasound is at frequencies greater than 20 kHz, and preferably in the range from 200 kHz to 3 MHz for applications that penetrate deep into the body. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves, the sonosensitizer is a porphyrin compound (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156 and Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-borne cancers (Paragraphs 0037-0038 of Chen).
Claims 12 and 20 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9, and 13 of U.S. Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Liu (PGPUB No. US 2018/0207447).
Regarding claim 12, modified US Patent No. 11,975,156 teaches the method in claim 7, as discussed above.
However, the combination of the claims of US Patent No. 11,975,156 and Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156 and Aubry with Liu’s teaching of the use of ALA for GBM treatment via SDT. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Regarding claim 20, modified US Patent No. 11,975,156 teaches the method in claim 13, as discussed above.
However, the combination of the claims of US Patent No. 11,975,156 and Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify US Patent No. 11,975,156 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT),
wherein the sonosensitizer is a porphyrin compound (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells (Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156 and Aubry with Liu’s teaching of treating GBM with ALA and PpIX to produce ROS for apoptosis. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claim 18 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-9, and 13 of U.S. Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872).
Regarding claim 18, modified US Patent No. 11,975,156 teaches the method in claim 14, as discussed above.
However, the combination of the claims of US Patent No. 11,975,156 and Aubry is silent regarding a method, further comprising administering microbubbles to the tumor cells,
wherein the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, further comprising administering microbubbles to the tumor cells (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1),
wherein the sonosensitizer is a porphyrin compound (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1. Paragraph 0171 teaches that there are apoptotic effects).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156 and Aubry with Callan’s teaching of administering microbubbles to tumors. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-9, and 13 of US Patent No. 11,975,156 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Hynynen et al. (PGPUB No. US 2018/0177491) further in view of Callan et al. (PGPUB No. US 2018/0344872).
Regarding claim 19, modified US Patent No. 11,975,156 teaches the method in claim 13, as discussed above.
However, the combination of the claims of US Patent No. 11,975,156 and Aubry is silent regarding a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse; and
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Hynynen teaches a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse (Fig. 14 shows sinusoidal ultrasound transmission. Fig. 17 shows sinusoidal signal with repeating peaks).It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156 and Aubry with Hynynen’s teaching of data transmission sets with sine waves. This modified method would allow for a user to have better focusing and steering range (Paragraph 0131 of Hynynen). Furthermore, the modified method would allow for less variability and improved correction of wave propagation (Paragraph 0131 of Hynynen).
However, Hynynen is silent regarding a method, wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the sonosensitizer is a porphyrin compound (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of US Patent No. 11,975,156, Aubry, and Hynynen with Callan’s teaching of administering microbubbles to tumors. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Claim 1-4 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, Claim 2 of copending Application No. 18/648807 teaches a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a patient interface configured for coupling to a skin surface of a head of a patient with a brain with tumor cells, the patient interface comprising an ultrasound transducer array and a cooling system, the cooling system comprising one or more cooling channels comprising independent loops forming a manifold around the skull, the manifold connecting an inlet tube and an outlet tube; and generating a signal to actuate the ultrasound transducer array; wherein the ultrasound transducer array comprises a plurality of ultrasound transducer elements, wherein the ultrasound transducer array is configured to emit acoustic waves having an acoustic intensity, wherein at least one of ultrasound transducers of the ultrasound transducer array is configured to emit a focused acoustic wave through the skull, wherein the patient interface is configured to acoustically couple the ultrasound transducer array to the skin surface, wherein the patient interface is configured for conforming to the skin surface, wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies to deliver the focused acoustic waves in the brain at the tumor cells of the patient; and circulating a fluid through the one or more cooling channels to reduce heat at the head of the patient at the patient interface (Claim 2 recites: A method of using acoustic waves for non-invasive sonodynamic therapy to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a patient with tumor cells, wherein the patient interface comprises a flexible membrane, wherein the flexible membrane is configured for acoustic coupling to an array of piezoelectric transducers via a fluid, wherein each of the piezoelectric transducers is configured to emit acoustic waves through the flexible membrane to the skin surface, driving the array of piezoelectric transducers with a signal, wherein the signal is frequency modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with one or more frequencies to modulate the acoustic waves to produce an acoustic intensity at the sonosensitizer to treat the tumor cells, wherein the signal is further duty cycle modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with a variety of different duty cycles thereby minimizing a spatial variation of the acoustic intensity at the tumor cells; and circulating the fluid through channels to reduce heat at the patient interface at the flexible membrane, wherein the channels are connected to an inlet tube and an outlet tube).
However, the claims of copending Application No. 18/648807 is silent regarding a method,
using focused acoustic waves and treatment of skull.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves and treatment of skull (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify copending Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 2, modified copending Application No. 18/648807 teaches the method in claim 1, as discussed above.
Claim 6 of copending Application No. 18/648807 further teaches a method, further comprising moving the patient interface with respect to the head of the patient (Claim 6 recites “wherein the patient interface is connected to a stand, and further comprising moving the patient interface with respect to the patient via the stand”).
Regarding claim 3, modified copending Application No. 18/648807 teaches the method in claim 1, as discussed above.
Claim 9 of copending Application No. 18/648807 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell, and a flexible shell (Claim 9 recites “wherein the array of piezoelectric transducers is attachable to a rigid shell”).
Regarding claim 4, modified copending Application No. 18/648807 teaches the method in claim 1, as discussed above.
Claim 8 of copending Application No. 18/648807 further teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Claim 8 recites “wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour”).
Claim 5 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Liu (PGPUB No. US 2018/0207447).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 5, modified Application No. 18/648807 teaches the method in claim 1, as discussed above.
However, the claims of Application No. 18/648807 is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method,
wherein the sonosensitizer is a porphyrin compound (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS),
wherein the focused acoustic waves are configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0049 teaches the use of protoporphyrins as sonosensitizers. Paragraph 0012 teaches that they are exerting the cytotoxic effect at an intended target site. Paragraph 0005 teaches that SDT involves the generation of ROS).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807 and Aubry with Callan’s teaching of the use of protoporphyrin for SDT. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
However, the combination of Application No. 18/648807, Aubry, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT. Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807, Aubry, and Callan with Liu’s teaching of the administration of ALA and the treatment of GBM. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claim 6 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872) further in view of Chen (PGPUB No. US 2009/0062724) further in view of Liu (PGPUB No. US 2018/0207447).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 6, modified Application No. 18/648807 teaches the method in claim 1, as discussed above.
However, the combination of the claims of Application No. 18/648807, Aubry, and Callan is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the ultrasound transducer array comprises a grid of elements, wherein the sonosensitizer is a porphyrin compound,
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2to activate the sonosensitizer.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the ultrasound transducer array comprises a grid of elements (Fig. 5 shows a grid of concentric flat ultrasound elements), wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT),
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807, Aubry, and Callan with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-born cancers (Paragraphs 0037-0038 of Chen).
However, Chen is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2to activate the sonosensitizer.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the sonosensitizer is a porphyrin compound (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the porphyrin compound becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT),
wherein the acoustic intensity is in a range of 0.1 W/cm2 to 50 W/cm2 to activate the sonosensitizer (Paragraph 0053 teaches that the ultrasound power is at 0.4 1 W/cm2 for the SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807, Aubry, Callan, and Chen with Liu’s teaching of SDT treatment with ALA and a specific acoustic energy. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claims 7-10 and 13-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 7, claim 2 of copending Application No. 18/648807 teaches a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a non-invasive sonodynamic therapy system configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells, wherein the non-invasive sonodynamic therapy system comprises: a patient interface, and a plurality of ultrasound transducers wherein each of ultrasound transducers of the plurality of ultrasound transducers is configured to emit a focused acoustic wave through the skull; driving the plurality of ultrasound transducers with a signal, modulating a duty-cycle of the signal to generate ultrasonic acoustic waves having an acoustic intensity; wherein the signal is configured to deliver the focused acoustic waves at a one or more frequencies with the acoustic intensity in the brain at the tumor cells of the patient, wherein the patient interface is configured to acoustically couple the plurality of ultrasound transducers to the skin surface of the head (Claim 2 recites: A method of using acoustic waves for non-invasive sonodynamic therapy to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a patient with tumor cells, wherein the patient interface comprises a flexible membrane, wherein the flexible membrane is configured for acoustic coupling to an array of piezoelectric transducers via a fluid, wherein each of the piezoelectric transducers is configured to emit acoustic waves through the flexible membrane to the skin surface, driving the array of piezoelectric transducers with a signal, wherein the signal is frequency modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with one or more frequencies to modulate the acoustic waves to produce an acoustic intensity at the sonosensitizer to treat the tumor cells, wherein the signal is further duty cycle modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with a variety of different duty cycles thereby minimizing a spatial variation of the acoustic intensity at the tumor cells; and circulating the fluid through channels to reduce heat at the patient interface at the flexible membrane, wherein the channels are connected to an inlet tube and an outlet tube).
However, the claims of copending Application No. 18/648807 is silent regarding a method, using focused acoustic waves and treatment of skull.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves and treatment of skull (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify copending Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 8, modified copending Application No. 18/648807 teaches the method in claim 7, as discussed above.
Claim 9 of copending Application No. 18/648807 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell, and a flexible shell (Claim 9 recites “wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell”).
Regarding claim 9, modified copending Application No. 18/648807 teaches the method in claim 7, as discussed above.
Claim 8 of copending Application No. 18/648807 further teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Claim 8 recites “wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour”).
Regarding claim 10, modified copending Application No. 18/648807 teaches the method in claim 7, as discussed above.
However, the claims of copending Application No. 18/648807 is silent regarding a method, wherein the signal is a pulse signal to pulse the focused acoustic waves to affect a spatial variation of the acoustic intensity in the brain at the tumor cells of the patient.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, wherein the signal is a pulse signal to pulse the focused acoustic waves to affect a spatial variation of the acoustic intensity in the brain at the tumor cells of the patient (Paragraph 0073 teaches that tumors can be treated. Figs. 1-2 show the treatment of the patient head. Paragraph 0077 teaches that the ultrasound waves can be forces in the patient head. Paragraph 0109 teaches the propagation of the waves at the points 18. Paragraph 0121 teaches that the spatial and time variation can be performed).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify copending Application No. 18/648807 with Aubry’s teaching of focusing ultrasound to vary the acoustic intensity. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 13, claim 2 of copending Application No. 18/648807 a method of using focused acoustic waves for non-invasive sonodynamic therapy through a skull to treat cells harboring a sonosensitizer, the method comprising: providing a patient interface configured to acoustically couple to a skin surface of a head of a patient with a brain with tumor cells, wherein the patient interface comprises at least one array of ultrasound transducer elements, wherein each ultrasound transducer elements of the at least one array of ultrasound transducer elements is configured to emit a focused acoustic waves through the skull; driving the at least one array of ultrasound transducer elements with a signal, modulating a duty-cycle of the signal to cause the focused acoustic waves to have an acoustic intensity with modulated duty cycle; wherein the signal is configured to deliver the acoustic intensity in the brain at the tumor cells of the patient (Claim 2 recites: A method of using acoustic waves for non-invasive sonodynamic therapy to treat cells harboring a sonosensitizer, the method comprising: acoustically coupling a patient interface to a skin surface of a patient with tumor cells, wherein the patient interface comprises a flexible membrane, wherein the flexible membrane is configured for acoustic coupling to an array of piezoelectric transducers via a fluid, wherein each of the piezoelectric transducers is configured to emit acoustic waves through the flexible membrane to the skin surface, driving the array of piezoelectric transducers with a signal, wherein the signal is frequency modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with one or more frequencies to modulate the acoustic waves to produce an acoustic intensity at the sonosensitizer to treat the tumor cells, wherein the signal is further duty cycle modulated to drive each of the piezoelectric transducers of the array of piezoelectric transducers with a variety of different duty cycles thereby minimizing a spatial variation of the acoustic intensity at the tumor cells; and circulating the fluid through channels to reduce heat at the patient interface at the flexible membrane, wherein the channels are connected to an inlet tube and an outlet tube).
However, the claims of copending Application No. 18/648807 is silent regarding a method, using focused acoustic waves and treatment of skull.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves and treatment of skull (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify copending Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
Regarding claim 14, modified copending Application No. 18/648807 teaches the method in claim 13, as discussed above.
Claim 13 of copending Application No. 18/648807 further teaches a method, wherein the focused acoustic waves comprise a frequency of 1 MHz (Claim 13 recites “wherein the one or more frequencies comprises a frequency in a range of 650 kHz to 2 MHz”).
Regarding claim 15, modified copending Application No. 18/648807 teaches the method in claim 13, as discussed above.
Claim 9 of copending Application No. 18/648807 further teaches a method, wherein the patient interface comprises at least one of a cap, a rigid shell and a flexible shell (Claim 9 recites “wherein the array of piezoelectric transducers is attachable to a rigid shell”).
Regarding claim 16, modified copending Application No. 18/648807 teaches the method in claim 13, as discussed above.
Claim 8 of copending Application No. 18/648807 further teaches a method, wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour (Claim 8 recites “wherein the non-invasive sonodynamic therapy lasts for 30 minutes to an hour”).
Claims 11 and 17 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824 in view of Chen (PGPUB No. US 2009/0062724).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 11, modified Application No. 18/648807 teaches the method in claim 7, as discussed above.
However, the combination of the claims of Application No. 18/648807 and Aubry is silent regarding a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method, wherein the focused acoustic waves deliver the non-invasive sonodynamic therapy at the one or more frequencies in a range of 20 kHz to 2 MHz to the tumor cells in the brain of the patient to activate the sonosensitizer (Paragraph 0092 teaches that the ultrasound is at frequencies greater than 20 kHz, and preferably in the range from 200 kHz to 3 MHz for applications that penetrate deep into the body. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer is a porphyrin compound (Paragraphs 0037-39 teach the use of porphyrin in SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807 and Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-borne cancers (Paragraphs 0037-0038 of Chen).
Regarding claim 17, modified Application No. 18/648807 teaches the method in claim 13, as discussed above.
Claim 13 of copending Application No. 18/648807 further teaches a method, wherein the focused acoustic waves comprise a frequency in a range of 20 kHz to 2 MHz (Claim 13 recites “wherein the one or more frequencies comprises a frequency in a range of 650 kHz to 2 MHz”).
However, the combination of the claims of Application No. 18/648807 and Aubry is silent regarding a method, wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves, the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Chen teaches a method,
wherein the focused acoustic waves comprise a frequency in a range of 20 kHz to 2 MHz (Paragraph 0092 teaches that the ultrasound is at frequencies greater than 20 kHz, and preferably in the range from 200 kHz to 3 MHz for applications that penetrate deep into the body. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves, the sonosensitizer is a porphyrin compound (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers. Paragraphs 0014 and 0016 teach the focus of ultrasound),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Paragraph 0092 teaches that the system produces ultrasound in a range between 200kHz and 3 MHz. The plurality of ultrasound elements 53 can be seen in Fig. 5. Abstract teaches that the system performs sonodynamic therapy (SDT). Paragraph 0089 teaches that the target tissue in the patient is cancerous tissue that has a sonodynamic agent present and made sensitive with ultrasound. Paragraph 0032 teaches that the sono-sensitizing compound that becomes cyto-toxic when exposed to ultrasound to treat cancers).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807 and Aubry with Chen’s teaching of a transmission of ultrasound waves with against porphyrin compounds and SDT. This modified method would provide a patient comfort (Paragraph 0091 of Chen). Furthermore, this modified method overcomes the failures of photodynamic therapy and allows for the treatment of deep tissues and blood-borne cancers (Paragraphs 0037-0038 of Chen).
Claim 12 and 20 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Liu (PGPUB No. US 2018/0207447).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 12, modified Application No. 18/648807 teaches the method in claim 7, as discussed above.
However, the combination of the claims of Application No. 18/648807 and Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient, wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807 and Aubry with Liu’s teaching of the use of ALA for GBM treatment via SDT. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Regarding claim 20, modified Application No. 18/648807 teaches the method in claim 13, as discussed above.
However, the combination of the claims of Application No. 18/648807 and Aubry is silent regarding a method, further comprising administering aminolevulinic acid (ALA) to the patient,
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain,
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves,
wherein the sonosensitizer is a porphyrin compound,
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding ultrasound treatment of tumors in the patient head, Aubry teaches a method, using focused acoustic waves (Paragraph 0077 teaches that the soundwaves are focus for emission by the transducer array at the patient brain).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify Application No. 18/648807 with Aubry’s teaching of using focused acoustic waves. This modified method would allow the user to non-invasively treat the patient brain and ensure that the array of the transducers is accurately positioned (Abstract of Aubry). Furthermore, the modification allows for the treatment of the patient cancers (Paragraph 0073 of Aubry).
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Liu teaches a method, further comprising administering aminolevulinic acid (ALA) to the patient (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the non-invasive sonodynamic therapy is for use to treat a glioblastoma multiforme (GBM) in the brain (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX. Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT),
wherein the sonosensitizer becomes cytotoxic upon exposure to the focused acoustic waves (Paragraph 0042-45 teaches the creation of cytotoxicity for GBM treatment and the use of SDT),
wherein the sonosensitizer is a porphyrin compound (Paragraph 0006 teaches the administration of ALA to the patient for GBM treatment as it is transformed to PpIX),
wherein the focused acoustic waves is configured to activate the porphyrin compound to produce a reactive oxygen species (ROS) thereby causing apoptosis of the tumor cells (Paragraph 0045 teaches that the PpIX in the GBM cells can result in the production of ROS based on the treatment and that causes apoptosis).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807 and Aubry with Liu’s teaching of treating GBM with ALA and PpIX to produce ROS for apoptosis. This modified method would allow for safe and efficacious treatments of cancer (Paragraph 0004 of Liu). Furthermore, the treatment reduces chances of recurrence and protects the surrounding healthy tissue to reduce side effects significantly (Paragraph 0059 of Liu).
Claim 18 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Callan et al. (PGPUB No. US 2018/0344872).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 18, modified Application No. 18/648807 teaches the method in claim 14, as discussed above.
However, the combination of the claims of Application No. 18/648807 and Aubry is silent regarding a method, further comprising administering microbubbles to the tumor cells,
wherein the sonosensitizer is a porphyrin compound,
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, further comprising administering microbubbles to the tumor cells (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1),
wherein the sonosensitizer is a porphyrin compound (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1),
wherein the signal is configured to activate the porphyrin compound thereby causing apoptosis of the tumor cells (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1. Paragraph 0171 teaches that there are apoptotic effects).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807 and Aubry with Callan’s teaching of administering microbubbles to tumors. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Claim 19 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 18/648807 in view of Aubry et al. (PGPUB No. US 2005/0277824) further in view of Hynynen et al. (PGPUB No. US 2018/0177491) further in view of Callan et al. (PGPUB No. US 2018/0344872).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 19, modified Application No. 18/648807 teaches the method in claim 13, as discussed above.
However, the combination of the claims of Application No. 18/648807 and Aubry is silent regarding a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse; and
wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding intra-cranial ultrasound transmission, Hynynen teaches a method, wherein the signal comprises at least one selected from the group consisting of: a sine wave, a rectangular pulse, and a triangular pulse (Fig. 14 shows sinusoidal ultrasound transmission. Fig. 17 shows sinusoidal signal with repeating peaks). It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807 and Aubry with Hynynen’s teaching of data transmission sets with sine waves. This modified method would allow for a user to have better focusing and steering range (Paragraph 0131 of Hynynen). Furthermore, the modified method would allow for less variability and improved correction of wave propagation (Paragraph 0131 of Hynynen).
However, Hynynen is silent regarding a method, wherein the sonosensitizer is a porphyrin compound.
In an analogous imaging field of endeavor, regarding SDT for cancer treatment, Callan teaches a method, wherein the sonosensitizer is a porphyrin compound (Abstract teaches that the microbubble is used with a chemotherapeutic agent complex. Paragraph 0049 teaches porphyrin as sonosensitizers. See Fig. 1).
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the combination of Application No. 18/648807, Aubry, and Hynynen with Callan’s teaching of administering microbubbles to tumors. This modified method would allow for improved efficacy of treatment and with greater targeting (Paragraph 0003 of Callan). Furthermore, the treatment improves survival rate and does not have adverse side effects (Paragraph 0010 of Callan).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Hynynen et al. (PGPUB No. US 2019/0021666): Teaches ultrasound focusing for cranial ultrasound transmission.
Liu et al. (PGPUB No. US 2012/0271165): Teaches ultrasound focusing for cranial ultrasound transmission.
Zeng et al. (PGPUB No. US 2012/0209150): Teaches ultrasound focusing for cranial ultrasound transmission.
Hynynen et al. (PGPUB No. US 2022/0233890): Teaches ultrasound focusing for cranial ultrasound transmission.
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 extension fee 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 date of this final action.
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/ADIL PARTAP S VIRK/Primary Examiner, Art Unit 3798
1 Link: https://www.fusfoundation.org/for-patients/how-it-works/
2 “Beamforming is defined as the technique of steering and focusing transmitted and received scanlines in ultrasound systems…” Link: https://www.sciencedirect.com/topics/physics-and-astronomy/beamforming
3 Link: https://www.uvahealth.com/treatments/focused-ultrasound
4 Link: https://radiopaedia.org/articles/beam-focusing?lang=us
5 Link: https://geekymedics.com/basics-of-ultrasound/