DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant’s arguments, filed on June 10, 2025 with respect to the rejection(s) of claim(s) 1-7, 9, 17, 21-22, and 24-27 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection have been made in view of Applicant’s amendments as can be further seen below.
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 (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claim 1-2, 6 and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Kroll et al. (Publication No. US 2005/0222646 A1, hereinafter Kroll) in view of Toth et al. (Publication No. US 2016/0029960 A1, hereinafter “Toth”), Ferek-Petric et al. (Publication No. US 2003/0204161 A1, hereinafter “Ferek”), and Ganz et al. (US 2004/0215296 A1, hereinafter “Ganz”, cited by Applicant). Kroll in view of Toth, Ferek, and Ganz is hereinafter referred to as “modified Kroll”.
Regarding claim 1, Kroll teaches a method for treating a cancerous tumor comprising:
implanting two or more leads (Figs. 2D (15)-(17), 2G (25)-(27), and para [0016] – first sentence) within a patient’s head, each of the two or more leads comprising one or more electric field generating electrodes (Figs. 2D, 2G, 22 (18)-(23) (86) and pars. [0070]: The devices and methods…are contemplated for use in numerous types of malignant tumors (i.e. cancer) and benign tumors…the devices and methods described herein are contemplated for use in…brain and central nervous system cancer (e.g. meningioma, astocytoma, oligodendrogliomas, ependymoma, gliomas, medulloblastoma, ganglioglioma, Schwannoma, germinoma, craniopharyngioma)…, [0106]: generator 1 with one or more electrodes…the electrodes 11 and 12 are implanted adjacent to the tumor 6 or …may be implanted into the tumor 6, [0159]: …driver 85, which provides electrical therapy to the lead electrodes 86) and one or more impedance monitoring electrodes (Figs. 22-23 (86) (91) and pars. [0159]: The driver circuit 85 delivers regulated voltage or constant current to the electrodes 86 to compensate for changes in impedance seen at the electrodes 86, [0160]: …sensor information from a tumor 6, such as tumor size, density, or chemistry data (e.g. pH) …can be detected by the electrodes 91 and specialized sensors such as…impedance…sensors, [0163], [0241]: … impedance and pH are related to the progression or regression of malignancies, and the impedance spectrum (i.e. the Z(f)) which is the impedance across the tumor at various frequencies, will allows estimation of tumor size);
measuring an impedance of tissue within the patient along a vector passing through a cancerous tumor (par. [0163]: …and the impedance spectrum (i.e. the Z(f)) which is the impedance across the tumor at various frequencies…);
administering an electric field to the cancerous tumor of the patient based on the measured impedance (pars. [0239], [0241]: In the case of sensed impedance, electrical therapy may be modified based on the impedance measured across or within the tumor…), and changes in an at least one property (pars. [0033]: …present invention can include modifying the applied electric power or current at least partially based on a detected characteristic or a change in a detected characteristic… modification of the applied electric power or current can occur in response to a measured …impedance, and the like, [0060]: A feedback unit 230 measures electric field delivery parameters and/or characteristics of the tissue of the target tissue region, measured parameters/characteristics including without limitation current, voltage, impedance, temperature modification of the applied electric power or current can occur in response to a measured temperature, impedance, and the like);
adjusting the electric field, including changing one or more of an amplitude, pulse width, and/or duty cycle (par. [0184]: Many parameters can be programmed such as duration of therapy, duty cycle, pulse width…), in response to a sensed impedance (par. [0241]: …sensed impedance, electrical therapy may be modified based on the impedance measured across or within the tumor as a function of frequency) where impedance is measured as a function of oxygen and the oxygen is an indication of growing tumor (par. [0241]: …increased oxygen may be indicative of growing tumors as they tend to have a large oxygen supply. Sensing oxygen for this purpose will allow electrical therapy to be adjusted accordingly).
The embodiments of Figs. 2D and 2G of Kroll are silent about impedance and impedance monitoring electrodes , however, in an envisioned embodiment, Kroll teaches controlling therapy based on sensed parameters including impedance across or within a tumor (par. [0239]) and that electrical therapy may be modified based on the impedance measured across or within the tumor (par. [0241]) to provide the benefit of numerous closed-loop approaches for use in electrical therapy (par. [0239]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to include in the two or more leads and electrodes of Figs. 2D and 2G, the embodiment of impedance sensing across or within a tumor, that includes both electric field generating electrodes and impedance monitoring electrodes on the leads, in order to provide the benefit of closed-loop approaches for use in electrical therapy.
While Kroll discloses the impedance is related to the progression or regression of tumor malignancies and size (Kroll, para [0163]), Kroll does not disclose that the decreased impedance across the treatment area is indicative of tumor progression.
However, Ganz in the same field of endeavor: treating abnormal tissue, discloses a measured decrease in impedance reflecting a lack of a decrease in the size of the tumor (para. [0058]: During the treatment the tissue impedance was monitored as an indicator of the progress of the treatment, high impedance being an indication of desiccation; a measure of high impedance is an indication that the tumor is shrinking, therefore a decrease in measured impedance would cause a lack of desiccation or shrinkage and hence a lack of decrease in size of the tumor) to provide the benefit of determining, through monitoring, tumor progression/regression using tissue impedance.
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method for treating a cancerous tumor using two or more leads by administering an electric field based on impedance measurements indicative of tumor growth, as taught by Kroll, to incorporate measuring a decrease in impedance that reflects a lack of desiccation or lack of decrease in tumor size, as taught by Ganz, in order to improve the status of the treatment in real time; and to provide the benefit of determining, through monitoring, tumor progression/regression using tissue impedance.
Although the combination of Kroll and Ganz teaches the impedance sensors and the impedance’s relationship to either the progression or regression of tumor malignancies and size, They do not explicitly disclose implanting one or more evoked potential sensors within the patient, the one or more evoked potential sensors configured to detect one or more electrical potential by a nervous system.
However, Toth, who is in the same field of endeavor, teaches: systems and methods for neuromodulation and controlled micro ablation procedures (see abstract, first two sentences). The system and method (figs. 1a-1d) teach implanting one or more evoked potential sensors within the patient, the one or more evoked potential sensors configured to detect one or more electrical potential by a nervous system (see para [0057] –“…monitoring one or more of…evoked potential, stimulation/sensing of nervous activity… to determine an anatomical map therefrom, a physiologic response to the stress test, or the like”).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method for treating a cancerous tumor, as taught by modified Kroll, to include evoked potential sensors of the nervous system as taught by Toth, in order to determine the properties of one or more neurological features in the vicinity of one or more monitoring sites.
Although Toth teaches implanting one or more evoked potential sensors, Toth does not explicitly disclose monitoring for one or more evoked potentials using the one or more evoked potential sensors to determine whether or not a strength of the electric field is above a threshold for neural or muscular recruitment, and, reducing the strength of the electric field if the electric field is above the threshold.
However, Ferek, who is in the same field of endeavor, teaches: systems and methods for electroporation treatment of subcutaneous tumors (see abstract, first sentence). The system/IMD (see figs. 2 & 3 – 204 and para [0039]) contain ECG circuitry (configured to measure an electrocardiogram) configured to sense a qR cardiac complex that is used to synchronize (such as adjusting and/or decreasing) electroporation therapy by providing High voltage (HV) pulses at or near the qR peak to avoid impeding normal cardiac rhythm (where the qR peak serves as the threshold point needed to reduce/adjust the strength of the electric field – see last two sentences of the abstract, para [0061]-[0063], and para [0068]-[0069]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the modified system of Kroll to contain the sensing and adjustment system of Ferek to arrive at the claimed invention. Such modification would lead to a reasonable expectation for success, since the modified system would allow for accurate sensing and stimulation adjustment in order to prevent adverse cardiac effects to the patient during tumor therapy treatment.
Regarding claim 2, modified Kroll teaches the method of claim 1, comprising administering electric field to the cancerous tumor of the patient based on changes in the measured impedance (Kroll, para [0159]: “The driver circuit 85 delivers regulated voltage or constant current to the electrodes 86 to compensate for changes in impedance seen at the electrodes 86, and para [0160]: …embodiments include …an index of tumor regression or proliferation… This type of information can be detected by the electrodes 91 and specialized sensors such as physical, impedance…sensors”).
Regarding claim 6, modified Kroll teaches the method of claim 1, further comprising monitoring for changes in the heart rate of the patient in response to the administered electric field; and
adjusting the electric field if changes in a heart rate of the patient are detected (Kroll, par. [0224]: Fig. 28b… … in response to an input from a microprocessor…changes may be in response to a sensor input, to …changes in measured heart rate variability).
Regarding claim 24, while modified Kroll teaches the method of claim 1, further comprising administering one or more electric fields to the cancerous tumor of the patient (Kroll, par. [0103]) based on the measured impedance (Kroll, pars. [0239], [0241]: In the case of sensed impedance, electrical therapy may be modified based on the impedance measured across or within the tumor…) and changes in the at least one property (pars. [0033], [0060]), and that the multiple electrodes may function in any combination of anodes and cathodes (Figs 2D-G 18, 19, 20, 21, 22, and 23 and par. [0107]-- the electric fields are produced along multiple vectors as electrodes function in any combination),
the examiner notes that Kroll does not explicitly disclose the vectors at least separated by 10 degrees.
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to contrive any number of desirable ranges for the degrees of vector separation disclosed by Applicant, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233. Further, it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980). Refer to MPEP §2144.05.
Regarding claim 25, modified Kroll teaches wherein the electric field is delivered using currents ranging from 1 mAmp to 1000 mAmp (Kroll, par. [0223]: …a therapeutic current level 143 of between 50 mA and 25 mA will be attained…).
Regarding claim 26, modified Kroll teaches the electric field is delivered using voltages ranging from 1 Vrms to 50 Vrms (Kroll, par. [0223]: …a therapeutic current level 143 of between…50 mV to 25 V will be attained… ).
Claims 3-5 are rejected under 35 U.S.C. 103 as being unpatentable over modified Kroll as applied to claims 1-2, 6 and 24-26 above, and further in view of Guo et al. (Publication No. US 2018/0154142 A1, hereinafter “Guo”).
Regarding claim 3, modified Kroll teaches the method of claim 1, except the electrodes comprising electric field generating electrodes and passive electric field sensing electrodes.
However, Guo in the same field of endeavor: methods and devices for treatment of tumors with nano-pulse stimulation, discloses the method of claim 1, the electrodes comprising electric field generating electrodes and passive electric field sensing electrodes (Fig. 3 and par. [0134] …an applicator tip with electrodes, which may be used in various embodiments of the present disclosure. In particular, an applicator tip 302 is shown that has one delivery electrode 304 and four ground electrodes 306 surrounding the delivery electrode 304; ground electrodes are considered sensing electrodes as the receive current and sense electrical activity) for the benefit of applying electrical pulses having certain parameters at a local tumor site in order to induce antitumor immunity and prevent distant metastases (par. [0125]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method of testing and treating a cancerous tumor, as taught by modified Kroll to include field generating as field sensing electrodes as taught by Guo, in order to provide the benefit of applying electrical pulses having certain parameters at a local tumor site in order to induce antitumor immunity and prevent distant metastases.
Regarding claim 4, while modified Kroll discloses the method of claim 3, further comprising implanting sensing electrodes within the cancerous tumor (Kroll, Fig. 2B and par. [0016]: The electrodes are implanted in or near the tumor…), the combination does not explicitly disclose the passive electric field sensing electrodes within the cancerous tumor.
However, Guo discloses implanting the passive electric field sensing electrodes within the cancerous tumor (Fig. 3 and par. [0139]: …one or more of the needle electrodes…penetrates the tumor…the needle electrodes 402 are configured to pierce the tumor) for the benefit of precisely applying the electrode to the tumor to conduct the electric pulses produced (par. [0139]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method for treating a cancerous tumor with implantable sensing electrodes of modified Kroll, to include implanted electric field sensing electrodes as taught by Guo in order to precisely applying the electrode to the tumor to conduct the electric pulses produced.
Regarding claim 5, modified Kroll teaches the method of claim 3, further comprising implanting the electrical field generating electrodes adjacent to the cancerous tumor (Kroll, Fig. 2C and par. [0106]: …the electrodes 11 and 12 are implanted adjacent to the tumor 6).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over modified Kroll as applied to claims 1-2, 6 and 24-26 above, and further in view of Palti (Publication No. US 2004/0176804 A1).
Regarding claim 7, modified Kroll discloses the method of claims 6, wherein adjusting the electric field comprises reducing a strength of the delivered electric field (Kroll, par. [0241]: If in the case that a high level of "free" or gaseous oxygen is measured, the system may be programmed to decrease the amount of current applied), but does not disclose reducing the strength to a predetermined threshold.
However, Palti discloses an apparatus and method for combating tumor growth (see abstract). The apparatus (fig. 2a) teaches applying a maximum optimal field strength that is less than the highest electric field strength focused at the targeted area, and therefore, optimizes the correlation between a calculated electric field and the desired electric field for the benefit of protecting the tissue area surrounding the tumor (par. [0138]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to combine the method for treating a cancerous tumor that decreases field strength in accordance with heart rate sensor input, as taught by modified Kroll with an optimal threshold strength as taught by Palti, in order protect the tissue area surrounding the tumor.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Kroll in view of Toth, Ferek, and Ganz (hereinafter referred to as “modified Kroll”), and further in view of Azure (Publication No. US 2009/0076500 A1).
Regarding claim 1, Kroll teaches a method for treating a cancerous tumor comprising:
implanting two or more leads (Figs. 2D (15)-(17), 2G (25)-(27), and para [0016] – first sentence) within a patient’s head, each of the two or more leads comprising one or more electric field generating electrodes (Figs. 2D, 2G, 22 (18)-(23) (86) and pars. [0070]: The devices and methods…are contemplated for use in numerous types of malignant tumors (i.e. cancer) and benign tumors…the devices and methods described herein are contemplated for use in…brain and central nervous system cancer (e.g. meningioma, astocytoma, oligodendrogliomas, ependymoma, gliomas, medulloblastoma, ganglioglioma, Schwannoma, germinoma, craniopharyngioma)…, [0106]: generator 1 with one or more electrodes…the electrodes 11 and 12 are implanted adjacent to the tumor 6 or …may be implanted into the tumor 6, [0159]: …driver 85, which provides electrical therapy to the lead electrodes 86) and one or more impedance monitoring electrodes (Figs. 22-23 (86) (91) and pars. [0159]: The driver circuit 85 delivers regulated voltage or constant current to the electrodes 86 to compensate for changes in impedance seen at the electrodes 86, [0160]: …sensor information from a tumor 6, such as tumor size, density, or chemistry data (e.g. pH) …can be detected by the electrodes 91 and specialized sensors such as…impedance…sensors, [0163], [0241]: … impedance and pH are related to the progression or regression of malignancies, and the impedance spectrum (i.e. the Z(f)) which is the impedance across the tumor at various frequencies, will allows estimation of tumor size);
measuring an impedance of tissue within the patient along a vector passing through a cancerous tumor (par. [0163]: …and the impedance spectrum (i.e. the Z(f)) which is the impedance across the tumor at various frequencies…);
administering an electric field to the cancerous tumor of the patient based on the measured impedance (pars. [0239], [0241]: In the case of sensed impedance, electrical therapy may be modified based on the impedance measured across or within the tumor…) and
adjusting the electric field, including changing one or more of an amplitude, pulse width, and/or duty cycle (par. [0184]: Many parameters can be programmed such as duration of therapy, duty cycle, pulse width…), in response to a sensed impedance (par. [0241]: …sensed impedance, electrical therapy may be modified based on the impedance measured across or within the tumor as a function of frequency) where impedance is measured as a function of oxygen and the oxygen is an indication of growing tumor (par. [0241]: …increased oxygen may be indicative of growing tumors as they tend to have a large oxygen supply. Sensing oxygen for this purpose will allow electrical therapy to be adjusted accordingly).
The embodiments of Figs. 2D and 2G of Kroll are silent about impedance and impedance monitoring electrodes , however, in an envisioned embodiment, Kroll teaches controlling therapy based on sensed parameters including impedance across or within a tumor (par. [0239]) and that electrical therapy may be modified based on the impedance measured across or within the tumor (par. [0241]) to provide the benefit of numerous closed-loop approaches for use in electrical therapy (par. [0239]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to include in the two or more leads and electrodes of Figs. 2D and 2G, the embodiment of impedance sensing across or within a tumor, that includes both electric field generating electrodes and impedance monitoring electrodes on the leads, in order to provide the benefit of closed-loop approaches for use in electrical therapy.
While Kroll discloses the impedance is related to the progression or regression of tumor malignancies and size (Kroll, para [0163]), Kroll does not disclose that the decreased impedance across the treatment area is indicative of tumor progression.
However, Ganz in the same field of endeavor: treating abnormal tissue, discloses a measured decrease in impedance reflecting a lack of a decrease in the size of the tumor (para. [0058]: During the treatment the tissue impedance was monitored as an indicator of the progress of the treatment, high impedance being an indication of desiccation; a measure of high impedance is an indication that the tumor is shrinking, therefore a decrease in measured impedance would cause a lack of desiccation or shrinkage and hence a lack of decrease in size of the tumor) to provide the benefit of determining, through monitoring, tumor progression/regression using tissue impedance.
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method for treating a cancerous tumor using two or more leads by administering an electric field based on impedance measurements indicative of tumor growth, as taught by Kroll, to incorporate measuring a decrease in impedance that reflects a lack of desiccation or lack of decrease in tumor size, as taught by Ganz, in order to improve the status of the treatment in real time; and to provide the benefit of determining, through monitoring, tumor progression/regression using tissue impedance.
Although the combination of Kroll and Ganz teaches the impedance sensors and the impedance’s relationship to either the progression or regression of tumor malignancies and size, They do not explicitly disclose implanting one or more evoked potential sensors within the patient, the one or more evoked potential sensors configured to detect one or more electrical potential by a nervous system.
However, Toth, who is in the same field of endeavor, teaches: systems and methods for neuromodulation and controlled micro ablation procedures (see abstract, first two sentences). The system and method (figs. 1a-1d) teach implanting one or more evoked potential sensors within the patient, the one or more evoked potential sensors configured to detect one or more electrical potential by a nervous system (see para [0057] –“…monitoring one or more of…evoked potential, stimulation/sensing of nervous activity… to determine an anatomical map therefrom, a physiologic response to the stress test, or the like”).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method for treating a cancerous tumor, as taught by modified Kroll, to include evoked potential sensors of the nervous system as taught by Toth, in order to determine the properties of one or more neurological features in the vicinity of one or more monitoring sites.
Although Toth teaches implanting one or more evoked potential sensors, Toth does not explicitly disclose monitoring for one or more evoked potentials using the one or more evoked potential sensors to determine whether or not a strength of the electric field is above a threshold for neural or muscular recruitment, and, reducing the strength of the electric field if the electric field is above the threshold.
However, Ferek, who is in the same field of endeavor, teaches: systems and methods for electroporation treatment of subcutaneous tumors (see abstract, first sentence). The system/IMD (see figs. 2 & 3 – 204 and para [0039]) contain ECG circuitry (configured to measure an electrocardiogram) configured to sense a qR cardiac complex that is used to synchronize (such as adjusting and/or decreasing) electroporation therapy by providing High voltage (HV) pulses at or near the qR peak to avoid impeding normal cardiac rhythm (where the qR peak serves as the threshold point needed to reduce/adjust the strength of the electric field – see last two sentences of the abstract, para [0061]-[0063], and para [0068]-[0069]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the modified system of Kroll to contain the sensing and adjustment system of Ferek to arrive at the claimed invention. Such modification would lead to a reasonable expectation for success, since the modified system would allow for accurate sensing and stimulation adjustment in order to prevent adverse cardiac effects to the patient during tumor therapy treatment.
Although Kroll as modified teaches wherein the electric field is generated at frequencies ranging from 100kHz to 5MHz (See Ferek, para [0066]), Kroll as modified does not explicitly disclose wherein the electric field is generated at frequencies selected from a range of between 10 kHz to 1MHz at the treatment area, wherein the electric field is effective to prevent and/or disrupt cellular mitosis in a cancerous cell.
However, Azure, in the same field of endeavor: electric field delivery and selective ablation of cancerous cells, discloses wherein the electric field is generated at frequencies selected from a range of between 10 kHz to 1MHz at the treatment area (par. [0050]: …the electrical current includes a frequency between about 50 kHz and about 300 kHz.), wherein the electric field is effective to prevent and/or disrupt cellular mitosis in a cancerous cell (par. [0048]…the electric field application as described was observed to be particularly effective in selectively disrupting and destroying the dividing cancerous cells, while having little or no effect on normal cells that were not exhibiting unregulated growth and proliferation…electric field application as described may specifically disrupt the cell division process (e.g., mitosis) or progression through the cell cycle, or a stage or process thereof…and, therefore, more particularly effects cells exhibiting unregulated growth (e.g., cancerous cells)…) for the purpose of preventing cancerous cells that progress more rapidly through the cell cycle (par. [0048]).
Examiner NOTES that “the electric field is effective to prevent and/or disrupt cellular mitosis in a cancerous cell” is intended use. Since Azure discloses the frequency range required it is capable of disrupt cellular mitosis of cancerous cells.
Therefore, It would have been obvious to one of ordinary skill in the art as of the filing date of Applicant' s invention to engage in routine experimentation to discover the optimal electric field range of 10kHz to 1MHz to provide proper disruption of cellular mitosis of cancerous cells. See MPEP § 2144.05(II)(A) (“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”) (citing In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Moreover, modifying the modified method of Kroll with the teachings of Azure would improve the system by improving the status of the treatment in real time to prevent cancerous cells from progressing more rapidly through the cell cycle.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Kroll in view of Azure (hereinafter referred to as “Modified Kroll 2”), in view of Toth and Ferek.
Regarding claim 17, Kroll teaches:
a method for treating a cancerous tumor comprising:
implanting two or more leads (Figs. 2D (15)-(17), 2G (25)-(27), para [0016] – first sentence, and para [0019]) within a patient, each of the two or more leads comprising one or more electric field generating electrodes (Figs. 2D, 2G, 22 (18)-(23) (86) and pars. [0070]: The devices and methods…are contemplated for use in numerous types of malignant tumors (i.e. cancer) and benign tumors…the devices and methods described herein are contemplated for use in…brain and central nervous system cancer (e.g. meningioma, astocytoma, oligodendrogliomas, ependymoma, gliomas, medulloblastoma, ganglioglioma, Schwannoma, germinoma, craniopharyngioma)…, [0106]: generator 1 with one or more electrodes…the electrodes 11 and 12 are implanted adjacent to the tumor 6 or …may be implanted into the tumor 6, [0159]: …driver 85, which provides electrical therapy to the lead electrodes 86) and one or more impedance monitoring electrodes (Figs. 22-23 (86) (91) and pars. [0159]: The driver circuit 85 delivers regulated voltage or constant current to the electrodes 86 to compensate for changes in impedance seen at the electrodes 86, [0160]: …sensor information from a tumor 6, such as tumor size, density, or chemistry data (e.g. pH) …can be detected by the electrodes 91 and specialized sensors such as…impedance…sensors, [0163], [0241]: … impedance and pH are related to the progression or regression of malignancies, and the impedance spectrum (i.e. the Z(f)) which is the impedance across the tumor at various frequencies, will allows estimation of tumor size), and
measuring an impedance of tissue within the patient along a vector passing through a cancerous tumor (par. [0163]: …and the impedance spectrum (i.e. the Z(f)) which is the impedance across the tumor at various frequencies…), but does not explicitly disclose
implanting one or more electric field sensing electrodes within the patient;
delivering an electric field from the electric field generating electrodes to apply an electric field therapy to a cancerous tumor;
measuring an electric field strength with the electric field sensing electrodes across the cancerous tumor; and
adjusting the delivered electric field to a desired electric field strength based on the measured electrical field strength.
However, Azure teaches methods and devices for electric field delivery for selective ablation of cancerous cells (see abstract, first sentence). The method (para 0005) teaches implanting one or more electric field sensing electrodes within the patient (par. [0055]: … non-thermal ablation according to the present invention can include placement of a sensor, such as a thermocouple, within the target tissue region (e.g., proximate to the inner electrode)…);
delivering an electric field from the electric field generating electrodes to apply an electric field therapy to a cancerous tumor (pars. [0036]: As set forth above, the electrode is positioned within the target tissue region and the applied electric field is sufficient to provide low-power or non-thermal/mild hyperthermic ablation of target cells, [0045]: As the electrode 86 is positioned within the target tissue region 88, the applied electrical current can provide an electric field that radiates outward and in a plurality of directions);
measuring an electric field strength with the electric field sensing electrodes across the cancerous tumor (Fig. 16 and par. [0060]: A feedback unit 230 measures electric field delivery parameters and/or characteristics of the tissue of the target tissue region, measured parameters/characteristics including without limitation current, voltage, impedance, temperature); and
adjusting the delivered electric field to a desired electric field strength based on the measured electrical field strength (Fig. 16 and par. [0060]: A feedback unit 230 measures electric field delivery parameters and/or characteristics of the tissue of the target tissue region, measured parameters/characteristics including without limitation current, voltage, impedance, temperature…modification of the applied electric power or current can occur in response to a measured temperature, impedance, and the like) for the benefit of precisely and accurately controlling energy delivery such that tissue hyperthermia can be accurately controlled and maintained in a desired temperature range selected for preferential destruction of cancerous cells compared to non-cancerous cells (par. [0036]), but does not disclose
implanting one or more evoked potential sensors within the patient, the one or more evoked potential sensors configured to detect one or more electrical potentials emitted by a nervous system.
However, Toth, who is in the same field of endeavor, teaches: systems and methods for neuromodulation and controlled micro ablation procedures (see abstract, first two sentences). The system and method (figs. 1a-1d) teaches implanting one or more evoked potential sensors within the patient, the one or more evoked potential sensors configured to detect one or more electrical potential by a nervous system (see para [0057] –“…monitoring one or more of…evoked potential, stimulation/sensing of nervous activity… to determine an anatomical map therefrom, a physiologic response to the stress test, or the like”).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method for treating a cancerous tumor, as taught by modified Kroll, to include evoked potential sensors of the nervous system as taught by Toth, in order to determine the properties of one or more neurological features in the vicinity of one or more monitoring sites.
Although Toth teaches implanting one or more evoked potential sensors, Toth does not explicitly disclose monitoring for one or more evoked potentials using the one or more evoked potential sensors to determine whether or not a strength of the electric field is above a threshold for neural or muscular recruitment, and, reducing the strength of the electric field if the electric field is above the threshold.
However, Ferek, who is in the same field of endeavor, teaches: systems and methods for electroporation treatment of subcutaneous tumors (see abstract, first sentence). The system/IMD (see figs. 2 & 3 – 204 and para [0039]) contain ECG circuitry (configured to measure an electrocardiogram) configured to sense a qR cardiac complex that is used to synchronize (such as adjusting and/or decreasing) electroporation therapy by providing High voltage (HV) pulses at or near the qR peak to avoid impeding normal cardiac rhythm (where the qR peak serves as the threshold point needed to reduce/adjust the strength of the electric field – see last two sentences of the abstract, para [0061]-[0063], and para [0068]-[0069]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the modified system of Kroll to contain the sensing and adjustment system of Ferek to arrive at the claimed invention. Such modification would lead to a reasonable expectation for success, since the modified system would allow for accurate sensing and stimulation adjustment in order to prevent adverse cardiac effects to the patient during tumor therapy treatment.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over modified Kroll as applied to claims 1-2, 6 and 24-26 above, and further in view of Fernandez (Publication No. US 2005/0043894 A1).
Regarding claim 22, modified Kroll discloses the method of claim 1, but does not disclose further comprising measuring a quantity of an analyte present in the treatment area, the analyte selected from the group consisting of fibrin, fibrinogen, immunoglobulins, deoxyribonucleic acids, ribonucleic acids, and bicarbonate.
However, Fernandez, in the same field of endeavor: integrated biosensor and simulation system for diagnosis and therapy, teaches measuring a quantity of an analyte present in the treatment area, the analyte selected from the group consisting of fibrin, fibrinogen, immunoglobulins, deoxyribonucleic acids, and ribonucleic acids (Fig. 2 and pars. [0050]: Sensor components may include deoxyribonucleic acid (DNA) sensor 201, ribonucleic acid (RNA) sensor 202, [0073]: …sensing techniques for cancer detection contemplated herein include…tests for cancer markers including…fibrin/fibrinogen) for the purpose of detecting condition of target tissue (par. [0005]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the method for treating a cancerous tumor, as taught modified Kroll to include tests and sensors for cancer markers, as taught by Fernandez, in order to detect the condition of target tissue.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over modified Kroll as applied to claims 1-2, 6 and 24-26 above, and further in view of Palti.
Regarding claim 27, modified Kroll discloses the method of claim 1, but does not teach wherein the electric field is delivered having a strength from 0.25 V/cm to 1000 V/cm.
However, Palti teaches wherein the strength of the electric field is delivered having a strength from 0.1V/cm to 10 V/cm (see para [0079] – emphasis on the last sentence), but does not teach wherein the electric field range goes up to 1000V/cm.
However, Ferek teaches wherein the electric field strength range goes from about 700 V/cm to about 1500 V/cm (see para [0070] – “HV pulses 414 may have most any electric field strength and pulse width that yield the desired electroporation characteristics. For example, electric field strengths of about 700 Volts/centimeter (V/cm) to about 1500 V/cm and pulse widths of about 50 microseconds to about 200 microseconds are possible.”)
Therefore, it would have been obvious to one of ordinary skill in the art as of the filing date of Applicant' s invention to engage in routine experimentation to discover the optimal range of 0.25 V/cm to 1000V/cm for the treatment strength range of the electric field. See MPEP § 2144.05(II)(A) (“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation”) (citing In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Furthermore, modifying the modified system of Kroll to contain the experimental range acquired from both Palti and Ferek would improve the method by allowing for proper termination and cancer cell inhibition within the target region.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Weaver (Patent No. 5,389,069) teaches a method and apparatus for causing electroporation of remote cells and tissue in vivo (see abstract – first sentence).
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARMEL J WEBSTER whose telephone number is (703)756-5960. The examiner can normally be reached Monday-Friday 7:30am-5:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, NIKETA PATEL can be reached at 571-272-4156. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/K.J.W./Examiner, Art Unit 3792
/NIKETA PATEL/Supervisory Patent Examiner, Art Unit 3792
Prosecution Insights