The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 7-13 and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Palti (US Patent Pub. No. 2006/0167499) in view of Wasserman (US Patent Pub. No. 2021/0203250).
Regarding claim 1, Palti discloses a method of selectively destroying or inhibiting the growth of rapidly dividing cells located within a target region of a subject’s body (see Title – “Treating a tumor or the like with electric fields at different orientations”, noting that tumors are “the growth of rapidly dividing cells” and the treating thereof is “destroying or inhibiting”), comprising the steps of:
Imposing an AC electric field in the target region with a field orientation that rotates with respect to the target region (see Abstract – “The selective destruction of rapidly dividing cells can therefore be accomplished by imposing an AC electric field in a target region… The field may also be rotated through 360o by applying AC waveforms with different phases to the electrodes.”), wherein the electric field has a frequency between 50 kHz and 1 MHz (see paragraph 27 – “The electronic apparatus includes a generator that generates an alternating voltage waveform at frequencies in the range from about 50 kHz to about 500 kHz.”).
However, Palti does not discuss patient discomfort or electro-sensation related to the initial onset of electric field applied to the patient, or specifically to an amplitude increase over the course of at least 0.1 seconds.
Wasserman teaches a high voltage, high efficiency sine wave generator that prevents spikes during amplitude adjustments and switching of channels (see Title). In paragraphs 137-139, there is a discussion related to Figures 14-16B. Particularly, Wasserman states that “FIG. 14 is a timing diagram that shows the sequencing between the two directions LR and AP that was used in the original Optune®.” Wasserman discusses the issue of switching when one sinusoid is at a peak, as illustrated in Figure 15. “Because such a spike 532 could cause the subject to experience an uncomfortable sensation, the original Optune® was designed to prevent such spikes from occurring. More specifically, this was accomplished by ramping down the output voltage of the AC voltage generator 20 from its steady-state value to zero V during the 100 ms interval that preceded each OFF state, then ramping the output voltage back up to its steady-state value during the 100 ms interval that followed each OFF state, as depicted in FIG. 16A, trace 540. The ramp rate was about 1 V/ms, which was sufficiently slow to avoid spikes that might be noticeable to a patient” (see paragraph 138, emphasis added). It is noted that “ramping the output voltage back up to its steady-state value during the 100 ms interval” means ramping up during a time period of 0.1s.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to provide a ramp up during a time period of 0.1 seconds, as taught by Wasserman, and to incorporate this into the channel switching generator in Palti in order to prevent the subject from experiencing an uncomfortable sensation (see paragraph 138 of Wasserman, as quoted above).
Regarding claim 2, Palti teaches that “the electric field intensity in the tissue to be treated is in the range of about 0.1 V/cm to about 10 V/cm” (see paragraph 90), which range includes 1 V/cm as claimed.
Regarding claim 3, Palti teaches that “the electric energy generated by the source reaches the vicinity of the body via a conductor and is transmitted from it through air or some other electric insulating material to the human body” (see paragraph 9). Additionally, paragraph 11 teaches that “the electric fields are high frequency alternating fields applied to the body by means of insulated electrodes.” Also see Figures 10 and 12, illustrating insulated electrodes.
Regarding claim 7, Palti teaches in paragraph 90 that “The generator 210 generates an alternating voltage waveform at frequencies in the range from about 50 kHz to about 500 kHz (preferably from about 100 kHz to about 300 kHz) (i.e., the TC fields)”, which range overlaps the range of 80 kHz to 300 kHz as claimed.
Regarding claim 8, Palti teaches that “in the case of glioma, field frequencies of 100, 150, 170, 200, 250, and 300 kHz may be applied during the first, second, third, fourth, fifth, and sixth minutes of treatment, respectively. That cycle of frequencies would then repeat during each successive six minutes of treatment” (see paragraph 126). This teaches that the AC electric field therapy is being applied for up to six minutes intervals, which means that the peak level is maintained for that period of time, even though the orientation of that field may be shifting within that time period. Viewed another way, the treatment being applied for six minutes results in a cumulative time period of greater than 100 seconds for which the final level is applied to the patient.
Regarding claim 9, Palti teaches that “Two approaches may be used to obtain a rotating field that rotates in a continuous manner (as opposed to a step-wise manner). One approach, which is usually not practical for in-vivo application, is to physically rotate the electrodes themselves. The other, more preferred, approach is to use 3 or more electrodes that surround the target region, and to simultaneously drive those electrodes with electric potentials in synchrony with one another, but with phase shifts between the driving signals” (see paragraph 165, emphasis added).
Regarding claim 10, it can be seen in Figure 16B of Wasserman that the ramp up period (and the ramp down period) are linear.
Regarding claim 11, Palti claims the following in claim 19:
“An apparatus for selectively destroying or inhibiting the growth of rapidly dividing cells located within a target region of a patient, the apparatus comprising:
at least three insulated electrodes, wherein each of the electrodes has a surface configured for placing against the patient's body; and
an AC voltage source having at least three outputs, each output being electrically connected to a respective one of the electrodes…”, which is identical to lines 1-7 of claim 11 with the addition of “insulated electrodes”.
In addition, Palti claims in claim 21 that “the frequency of the electric field is between about 50 kHz and about 500 kHz”, which overlaps with the claimed range of 50 kHz – 1 MHz.
However, Palti does not discuss patient discomfort or electro-sensation related to the initial onset of electric field applied to the patient, or specifically to an amplitude increase over the course of at least 0.1 seconds, nor that the final level is 50 V RMS.
Wasserman teaches a high voltage, high efficiency sine wave generator that prevents spikes during amplitude adjustments and switching of channels (see Title). In paragraphs 137-139, there is a discussion related to Figures 14-16B. Particularly, Wasserman states that “FIG. 14 is a timing diagram that shows the sequencing between the two directions LR and AP that was used in the original Optune®.” Wasserman discusses the issue of switching when one sinusoid is at a peak, as illustrated in Figure 15. “Because such a spike 532 could cause the subject to experience an uncomfortable sensation, the original Optune® was designed to prevent such spikes from occurring. More specifically, this was accomplished by ramping down the output voltage of the AC voltage generator 20 from its steady-state value to zero V during the 100 ms interval that preceded each OFF state, then ramping the output voltage back up to its steady-state value during the 100 ms interval that followed each OFF state, as depicted in FIG. 16A, trace 540. The ramp rate was about 1 V/ms, which was sufficiently slow to avoid spikes that might be noticeable to a patient” (see paragraph 138, emphasis added). It is noted that “ramping the output voltage back up to its steady-state value during the 100 ms interval” means ramping up during a time period of 0.1s.
Additionally, it is noted that in Figure 16B, the peak voltage is +/- 80 volts. The AC voltage shown in Figure 16B of Wasserman equates to approximately 56.57 V RMS, based on the RMS Voltage Calculator at https://www.omnicalculator.com/physics/rms-voltage with “Characteristic Voltage” set to “Peak Voltage (Vp)”, “Voltage” set to “80”, and “Wave Offset (V0)” set to zero.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to provide a ramp up during a time period of 0.1 seconds, as taught by Wasserman, and to incorporate this into the channel switching generator in Palti in order to prevent the subject from experiencing an uncomfortable sensation (see paragraph 138 of Wasserman, as quoted above).
Regarding claim 12, Palti teaches that “in the case of glioma, field frequencies of 100, 150, 170, 200, 250, and 300 kHz may be applied during the first, second, third, fourth, fifth, and sixth minutes of treatment, respectively. That cycle of frequencies would then repeat during each successive six minutes of treatment” (see paragraph 126). This teaches that the AC electric field therapy is being applied for up to six minutes intervals, which means that the peak level is maintained for that period of time, even though the orientation of that field may be shifting within that time period. Viewed another way, the treatment being applied for six minutes results in a cumulative time period of greater than 30 seconds for which the final level is applied to the patient.
Regarding claim 13, discusses dielectric constants in paragraph 96, including discussions of various thicknesses creating different dielectric constants such as 2-3, or some as much as 20-50. Then, in paragraph 99 Palti states “Since the thin insulating layer can be very vulnerable, etc., the insulation can be replaced by very high dielectric constant insulating materials, such as titanium dioxide (e.g., rutile), the dielectric constant can reach values of about 200. There a number of different materials that are suitable for use in the intended application and have high dielectric constants.” This teaching of using titanium dioxide and achieving a “dielectric constant [that] can reach values of about 200” reads on “insulating material having a dielectric constant of at least 20”, as claimed. It is also re-iterated that claim 19 of Palti teaches electrodes, which inherently have a conductive substrate, and that they are “insulated electrodes”.
Regarding claim 16, Palti teaches in paragraph 90 that “The generator 210 generates an alternating voltage waveform at frequencies in the range from about 50 kHz to about 500 kHz (preferably from about 100 kHz to about 300 kHz) (i.e., the TC fields)”, which range overlaps the range of 80 kHz to 300 kHz as claimed.
Regarding claim 17, Palti teaches the following in paragraph 168, “For example, three electrodes may be physically positioned around the target mass spaced 120o apart, and driven by three sinusoids that are phase-shifted by 120o with respect to each other … to create a similar rotating field.”
Regarding claim 18, Palti teaches in paragraphs 166-167 and with regard to Figure 32A, “Assuming that we have a body 1610 containing a target mass 1612, a preferred placement for the electrodes is to place a first pair one pair of electrodes 1620 on opposite sides of the body 1610, and another pair of electrodes 1630 on opposite sides of the body 1610, offset by 90o from the first set of electrodes 1620. … When both sets of outputs are sinusoids with the same frequency and the first set of outputs is shifted in phase by 90o from the second set of outputs, the field will rotate in the target area 1612 within the body 1610.”
Regarding claim 19, it is noted that claim 27 of Palti states, nearly verbatim, the limitations of claim 19. Aside from the claim language of Palti, Palti teaches “FIG. 33 depicts another set of waveforms that can be used to rotate the field, for the same electrode arrangement that is shown FIG. 32A. In this case the voltage sources produce alternating waveforms 1670, 1680, the amplitude of each being modulated at some chosen frequency that is much lower than the frequency of the waveforms being modulated. The two modulating waveforms 1675, 1685 are provided with a phase shift between them.” When looking at Figure 33, it can be seen that the modulating waveforms 1675, 1685 is “at least ten times lower” frequency than the waveforms being modulated 1670, 1680.
Regarding claim 20, it can be seen in Figure 16B of Wasserman that the ramp up period (and the ramp down period) are linear.
Claims 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Palti in view of Wasserman as applied to claim 1 above, and further in view of Armstrong (US Patent Pub. No. 2007/0097593).
Regarding claim 4, Palti in combination with Wasserman is described above with regard to claim 1. While Palti teaches a rotating electric field via electrodes located around a periphery of a patient’s torso or limb, and Wasserman teaches a ramp up and ramp down period between the transition of each electrode, the stated time period of the ramp up/down in Wasserman is not taught as being greater than 0.1 s.
Armstrong teaches variable output ramping for an implantable medical device (see Title). Similar to Wasserman, Armstrong teaches a ramping-up portion and a ramping-down portion with a therapeutic portion therebetween (see Figure 2), which is provided for the same reasons as Wasserman (i.e., “a sudden initiation of an electrical signal may cause an undesired reaction or side effect (e.g., pain)” – see paragraph 5). “FIG. 6A illustrates a ramp-up signal portion that has a first duration (e.g., a 3 second duration). In this example, the latter portion of the duration may necessitate a "tapering-off" in the slope of the rate-of-rise. FIG. 6B illustrates a ramp-up signal portion that has a shorter duration (e.g., a 1 second duration)” (see paragraph 59).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to utilize a ramping-up portion for a time period sufficient to reach a therapeutic stimulation signal without causing discomfort to the patient whether it be 0.1 second (as in Wasserman) or 1 second or 3 seconds (as taught in Armstrong), as this would have been obvious to try a length of time greater than 0.1 seconds since the result of pain or sensation would occur with a faster ramp up time, not a slower ramp up time (“in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions” – see MPEP 2144.05(II)(B)).
Regarding claim 5, Palti teaches that “the electric field intensity in the tissue to be treated is in the range of about 0.1 V/cm to about 10 V/cm” (see paragraph 90), which range includes 5 V/cm as claimed.
Regarding claim 6, Palti teaches that “the electric field intensity in the tissue to be treated is in the range of about 0.1 V/cm to about 10 V/cm” (see paragraph 90), which range includes 5 V/cm as claimed. Additionally, paragraph 90 of Palti teaches that “The generator 210 generates an alternating voltage waveform at frequencies in the range from about 50 kHz to about 500 kHz (preferably from about 100 kHz to about 300 kHz) (i.e., the TC fields)”, which range overlaps the range of 80 kHz to 300 kHz as claimed. With regard to the claim limitation of a ramp up time of at least 0.3 seconds, it is re-iterated that the addition of Armstrong teaches a ramp up time of greater than 0.3 seconds.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Palti in view of Wasserman and Armstrong, and further in view of Lee et al. (US Patent Pub. No. 2021/0308476).
Regarding claim 4, Palti in combination with Wasserman and Armstrong is described above with regard to claim 4. Palti teaches a rotating electric field via electrodes located around a periphery of a patient’s torso or limb; Wasserman teaches a ramp up and ramp down period between the transition of each electrode and explicitly shows a final level of 80 V in Figure 16B; and Armstrong teaches alternative time periods for the ramp up; however, none of these references explicitly teach a final level of at least 100 V RMS.
Lee teaches “a cancer treatment device which includes a first electrode and a second electrode, which are electrically connected to a signal generator and face each other with a target area therebetween… A cancer cell is present in the target area. The signal generator applies an AC voltage between the first electrode and the second electrode to generate an electric field between the first electrode and the second electrode” (see Abstract). In paragraph 41, Lee teaches that “The control unit 102 may determine an amplitude, a frequency, etc. of the waveform transmitted from the waveform generating unit 101. … The amplitude of the waveform may be determined as greater than about 0 V/cm and less than or equal to about 100 V/cm.”
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to utilize a final level of 100 V/cm, as taught by Lee, with the system and methods of Palti as combined with Wasserman and Armstrong, since it has been held that discovering the optimum or workable ranges involves only routine skill in the art (In re Aller, 105 USPQ 233 – see MPEP 2144.05 (II)(A)).
Regarding claim 15, Palti teaches in paragraph 90 that “The generator 210 generates an alternating voltage waveform at frequencies in the range from about 50 kHz to about 500 kHz (preferably from about 100 kHz to about 300 kHz) (i.e., the TC fields)”, which range overlaps the range of 80 kHz to 300 kHz as claimed.
Conclusion
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/JAMES KISH/ Primary Examiner, Art Unit 3792