DETAILED ACTION
This Office action is in response to the request for continued examination filed on March 17th, 2026. Claims 1, 4-15 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 .
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.
Claim(s) 1, 4-5, 7-9, and 12-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0250528 (Liu et al.).
Regarding claim 1, Liu et al. discloses a neutron capture therapy device, comprising
a neutron beam irradiation system configured to generate a neutron beam (fig. 3, elements 10 and T),
a detection system configured to detect irradiation parameters (fig. 3, element 60), and
a monitoring system configured to control the whole neutron beam irradiation process (fig. 3, element 70) and comprising
a control part configured to perform a therapy plan according to the irradiation parameters (‘the charged particle beam is adjusted and the irradiation dose is controlled.’ P 14), and
a correction part configured to correct a part of the irradiation parameters (‘The detection method further includes a calculation step for calculating the intensity of the neutron beam according to detection signal, so that the charged particle beam is adjusted and the irradiation dose is controlled.’ P 23), wherein the irradiation parameters comprise a remaining irradiation time (‘irradiation dose is controlled.’ P 14, where it is understood that this will require controlling both the irradiation time and intensity).
Liu et al. does not specifically disclose a storage part configured to store the irradiation parameters. However, control systems commonly include a memory for storing the irradiation parameters and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to include such a storage so that the parameters could be stored for easy access when control needs them.
Liu et al. also does not disclose whether the correction part corrects the remaining irradiation time by setting the remaining irradiation time to
t
r
=
D
t
o
t
a
l
-
D
c
o
m
p
l
e
t
e
d
D
-
and
D
-
=
D
c
o
m
p
l
e
t
e
d
t
where t is an implemented radiation time,
D
-
is an average neutron doseage value in a period of t, Dcompleted is the portion of the neutron dosage that has already beam completed, and Dtotal is a preset neutron dosage.
Liu et al. discloses controlling the dose by adjusting the charged particle beam (‘the charged particle beam is adjusted and the irradiation dose is controlled.’ P 14), and the dose is a product of the irradiation time and the intensity, therefore it would have been obvious to a person having ordinary skill in the art at the time the application was filed to adjust the beam by adjusting either the irradiation time or the intensity or a combination because these are the only known means of adjusting the beam to control the dose. Liu discloses that the real-time doseage is detected (‘the radiation detection system calculates the intensity of the neutron beam according to detection signal’ P 14). Inputting this into the equations above will result in correction of the remaining irradiation time to account for the actual beam doseage. Note that the equations express in mathematical terms that the remaining time is the difference between the total time and the time that has already elapsed, where the time that has elapsed is expressed as a function of dose and intensity using the relationship of dose = intensity X time.
Regarding claim 4, Liu et al. discloses the neutron capture therapy device of claim 1, wherein the irritation parameters further comprise a neutron dosage rate (‘irradiation dose is controlled.’ P 14, where it is understood that this will require controlling the irradiation time and intensity). Liu et al. does not disclose whether the correction part corrects the neutron dosage rate. Liu et al. discloses controlling the dose by adjusting the charged particle beam (‘the charged particle beam is adjusted and the irradiation dose is controlled.’ P 14), and the dose is a product of the irradiation time and the intensity, therefore it would have been obvious to a person having ordinary skill in the art at the time the application was filed to adjust the beam by adjusting either the irradiation time or the intensity or a combination because these are the only known means of adjusting the beam to control the dose.
Regarding claim 5, Liu et al. discloses the neutron capture therapy device of claim 4, wherein the corrected neutron dosage rate Ir is calculated by using a formula (2-5):
I
r
=
D
t
o
t
a
l
-
D
r
t
o
-
t
(2-5) where t is an implemented irradiation time, t0 is a preset irradiation time, Dr is a real-time neutron dosage detected by the detection system, and Dtotal is a preset neutron dosage (detection of real-time neutron dosage shown by ‘the radiation detection system calculates the intensity of the neutron beam according to detection signal’ P 14, the equation itself simply expresses updating the rate to what is needed to maintain the same total dose since rate = dose/time).
Regarding claim 7, Liu et al. discloses the neutron capture therapy device of claim 1, wherein the irradiation parameters further comprise preset irradiation parameters, real-time irradiation parameters and corrected irradiation parameters, and the monitoring system further comprises
an input part configured to input the preset irradiation parameters (obvious to include an input part so that desired dose could be set by operator),
a reading part configured to read the real-time irradiation parameters detected by the detection system (‘detection device is used for real-time detection’ abstract, where reading the detection signal is inherent in the use of it by the calculation part),
a calculation part configured to calculate the irradiation parameters stored in the storage part (‘the radiation detection system calculates the intensity of the neutron beam according to detection signal, so that the charged particle beam is adjusted and the irradiation dose is controlled.’ P 14),
a display part configured to display at least the remaining irradiation time of the irradiation parameters in real time (fig. 3, element 72).
Liu et al. does not disclose a determination part configured to determine, according to a calculation result of the calculation part, whether the irradiation parameters are needed to be corrected. Liu et al. does disclose a correction part for correcting the irradiation parameters based on the calculation result (fig. 3, element 71). It would have been obvious to a person having ordinary skill in the art at the time the application was filed to include a determination part to determine whether the irradiation parameters are needed to be corrected to reduce computational burden by ensuring that such correction is only carried out when needed.
Regarding claim 8, Liu et al. discloses the neutron capture therapy device of claim 7, wherein before the preset irradiation parameters are corrected, the storage part stores the preset irradiation parameters (intended use and obvious to store for the reasons stated above), and the remaining irradiation time displayed by the display part is a difference value between the preset irradiation time and an actually implemented irradiation time (intended use, also this is just displaying remaining irradiation time, which is by definition the difference between the total time and the elapsed time, which is obvious so that operator can see how much time remains); and after the preset irradiation parameters are corrected, the storage part stores latest corrected irradiation parameters (intended use, also obvious to store corrected value for easy access by control), and the remaining irradiation time displayed by the display part is the corrected remaining irradiation time (intended use, also obvious to display the corrected time so the operator can see the correct time).
Regarding claim 9, Liu et al. discloses the neutron capture therapy device of claim 8, wherein in response to a difference value between the real-time irradiation parameter and the preset irradiation parameter calculated by the calculation part gives an instruction of correcting the irradiation parameters (‘More particularly, the radiation detection device is an ionization chamber or a scintillator, the radiation detection system calculates the intensity of the neutron beam according to detection signal, so that the charged particle beam is adjusted and the irradiation dose is controlled.’ P 14).
Liu et al. does not disclose comparing the difference to a first, second, or third threshold. Comparing differences to thresholds to determine if correction is warranted is common in the art, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the device of Liu et al. to correct the irradiation parameters when the difference is greater than a first threshold because larger differences indicate greater need to correct.
Regarding claim 12, Liu et al. discloses an operation method of the monitoring system of the neutron capture therapy device of claim 7, comprising:
S1: inputting, by the input part, the preset irradiation parameters (obvious to input so that an initial parameter set can be used for control);
S2: storing, by the storage part, the irradiation parameters (obvious to store so that the parameters are saved);
S3: performing, by the control part, the therapy plan according to the irradiation parameters stored in the storage part (‘irradiation dose is controlled’ P 14);
S4: reading, by the reading part, the real-time irradiation parameters detected by the detection system (inherent in the calculating step);
S5: calculating, by the calculation part, the irradiation parameters stored in the storage part and the real-time irradiation parameters read by the reading part (‘the radiation detection system calculates the intensity of the neutron beam according to detection signal’ P 14);
S7: correcting, by the correction part, a latest set of irradiation parameters in the storage part (‘so that the charged particle beam is adjusted and the irradiation dose is controlled.’ P 14); and
Liu et al. does not disclose S6: determining, by the determination part, whether the irradiation parameters stored in the storage part are needed to be corrected, according to the calculation result of the calculation part; or performing the correcting in response to the determination part determining to correct the irradiation parameters stored in the storage part; not performing, by the correction part, a correction action, in response to the determination part determining not to correct the latest set of irradiation parameters. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to include such a determination step and perform or not perform the correction based on the determination step to reduce computational burden by ensuring that such correction is only carried out when needed.
Liu et al. also does not disclose S8: displaying, by the display part, the remaining irradiation time in real time according to the latest set of irradiation parameters stored in the storage part. Liu et al. does disclose feeding the result to a display unit, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to display the remaining irradiation time so the operator knows how long the irradiation should last.
Regarding claim 13, Liu et al. discloses the operation method of the monitoring system of the neutron capture therapy device of claim 12, wherein before the preset irradiation parameters are corrected, the storage part stores the preset irradiation parameters (obvious to store so that the parameters are saved), and the display part displays the remaining irradiation time and other preset irradiation parameters in real time (this is just displaying remaining irradiation time, which is already claimed, remaining irradiation time is by definition the difference between the total time and the elapsed time); and after the preset irradiation parameters are corrected, the storage part stores a latest set of corrected irradiation parameters (obvious to store corrected value for easy access by control), and the display part displays the corrected remaining irradiation time and the latest set of other corrected irradiation parameters in real time (obvious to display the corrected time so the operator can see the correct time).
Claim(s) 6, 10-11, and 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. as applied to claim 3 above, and further in view of WO 2018/205403 (the ‘403 publication).
Regarding claim 6, the ‘403 publication discloses a neutron capture therapy device with a correction part configured to correct the remaining irradiation time (fig. 7, element 270), wherein the irradiation parameters comprise a boron concentration, and the correction part corrects the boron concentration (‘the feedback unit generates a feedback signal of a concentration of the calculated boron (10B) to the neutron capture therapy device in real time.’ P 20). It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the therapy device of Liu et al. to include storing and correcting the boron concentration because the boron concentration effects the tumor site dose, as known to Liu et al. (‘The epithermal neutron intensity and the concentration of the boronated pharmaceuticals at the tumor site codetermine clinical therapy time.’ P 41) and correcting the boron concentration as done in the ‘403 publication allows for adjusting the total dose to ensure that the tumor specific dose is as desired.
Regarding claim 10, Liu et al. disclose the neutron capture therapy device of claim 1, wherein the detection system comprises a neutron dosage detection device configured to detect the real-time neutron dosage in real time (‘the radiation detection system calculates the intensity of the neutron beam according to detection signal’ P 14).
Liu et al. does not disclose a temperature detection device configured to detect temperature of the neutron beam irradiation system, a displacement detection device configured to detect whether an object to be irradiated generates displacement during therapy, and a boron concentration detection device configured to detect a boron concentration in a body of the object to be irradiated.
The ‘403 publication discloses a boron concentration detection device configured to detect a boron concentration in a body of the object to be irradiated (fig. 7, element 200). It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the device of Liu et al. to include the boron concentration detection device of the ‘403 publication because the boron concentration effects the tumor site dose, as known to Liu et al. (‘The epithermal neutron intensity and the concentration of the boronated pharmaceuticals at the tumor site codetermine clinical therapy time.’ P 41) and measuring the boron concentration allows for correction of the irradiated dose to ensure the tumor specific dose is as needed.
Temperature and displacement detection devices are well-known in the art, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the therapy device of Liu et al. to include a temperature detection device so that target overheating could be detected and prevented, and further obvious to include a displacement detection device so that tumor location could be verified and therapy carried out at the appropriate location.
Regarding claim 11, Liu et al. in view of the ‘403 publication discloses the neutron capture therapy device of claim 10, wherein the neutron dosage detection device comprises a detector configured to receive the neutron beam and output a signal, a signal processing unit configured to process the signal output from the detector, a counter configured to count a signal output from the signal processing unit to obtain a counting rate a conversion unit configured to convert the counting rate recorded by the counter into a neutron flux rate or a neutron dosage rate, an integration unit configured to integrate the neutron flux rate or the neutron dosage rate to obtain the neutron dosage (‘A common radiation detection device for real-time detection may have two different detection principles, namely an ionization chamber and a scintillator detector, can be realized. Those adopting ionization chamber structures as substrates include an He-3 proportional counter, a BF3 proportional counter, a fission chamber and a boron ionization chamber. The scintillator detector may be divided into organic and inorganic materials, and for the purpose of detecting thermal neutrons, the scintillator detector mainly adds high thermal neutron capture section elements such as Li or B. In short, most of neutron energies detected by this type of detectors are the thermal neutrons, which are all heavy charged particles and nuclear fission fragments released by means of a capture or nuclear fission reaction between elements and neutrons, a great number of ion pairs are generated in the ionization chamber or the scintillator detector, and after the charges are collected, a current signal may be converted into a voltage pulse signal via appropriate circuit conversion.’ P 15), and a display configured to display the neutron dosage (fig. 3, element 72).
Regarding claim 14, Liu et al. in view of the ‘403 publication disclose an operation method of the monitoring system of the neutron capture therapy device of claim 10, comprising:
S1: inputting, by the input part, the preset irradiation parameters (obvious to input so that an initial parameter set can be used for control);
S2: storing, by the storage part, the irradiation parameters (obvious to store so that the parameters are saved);
S3: performing, by the control part, the therapy plan according to the irradiation parameters stored in the storage part (‘irradiation dose is controlled’ P 14);
S4: reading, by the reading part, the real-time irradiation parameters detected by the detection system (inherent in the calculating step);
S5: calculating, by the calculation part, the irradiation parameters stored in the storage part and the real-time irradiation parameters read by the reading part (‘the radiation detection system calculates the intensity of the neutron beam according to detection signal’ P 14);
S7: correcting, by the correction part, a latest set of irradiation parameters in the storage part (‘so that the charged particle beam is adjusted and the irradiation dose is controlled.’ P 14); and
Liu et al. does not disclose S6: determining, by the determination part, whether the irradiation parameters stored in the storage part are needed to be corrected, according to the calculation result of the calculation part; or performing the correcting in response to the determination part determining to correct the irradiation parameters stored in the storage part; not performing, by the correction part, a correction action, in response to the determination part determining not to correct the latest set of irradiation parameters. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to include such a determination step and perform or not perform the correction based on the determination step to reduce computational burden by ensuring that such correction is only carried out when needed.
Liu et al. also does not disclose S8: displaying, by the display part, the remaining irradiation time in real time according to the latest set of irradiation parameters stored in the storage part. Liu et al. does disclose feeding the result to a display unit, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to display the remaining irradiation time so the operator knows how long the irradiation should last.
Regarding claim 15, Liu et al. in view of the ‘403 publication discloses the operation method of the monitoring system of the neutron capture therapy device of claim 14, wherein before the preset irradiation parameters are corrected, the storage part stores the preset irradiation parameters (obvious to store so that the parameters are saved), and the display part displays the remaining irradiation time and other preset irradiation parameters in real time (this is just displaying remaining irradiation time, which is already claimed, remaining irradiation time is by definition the difference between the total time and the elapsed time); and after the preset irradiation parameters are corrected, the storage part stores a latest set of corrected irradiation parameters (obvious to store corrected value for easy access by control), and the display part displays the corrected remaining irradiation time and the latest set of other corrected irradiation parameters in real time (obvious to display the corrected time so the operator can see the correct time).
Response to Arguments
Applicant's arguments filed March 17th, 2026 have been fully considered but they are not persuasive.
Applicant points out examiners sloppy use of the scalar term flux rather than the vector term intensity in discussing the relationship between dose and irradiation parameters. Applicant is quite right that the dose will only include that portion of the flux within the solid angle range that allows it to be absorbed by the detector or tissue. The terms flux and intensity are sometimes used interchangeably in casual parlance but examiner should have been more careful. Examiner has corrected the terminology in the rejection above to refer to intensity.
Applicant argues that while Liu does not explicitly disclose how the beam is adjusted, it is clear that they adjust the intensity rather than the irradiation time because they disclose adjusting the dose by controlling the accelerator, and a person having ordinary skill in the art would understand that the intensity of the beam can be controlled by adjusting the accelerator.
Examiner agrees a person having ordinary skill in the art would understand that the intensity could be changed by adjusting the operation of the accelerator. Examiner contends, however, that a person having ordinary skill in the art would also understand that the irradiation time could be controlled by adjusting the accelerator. Specifically, a person having ordinary skill in the art would understand that the irradiation time could be controlled by controlling when particles within the accelerator are ejected towards the target. Alternatively, if the accelerator does not feed other beamlines, the irradiation time could be controlling simply by turning the accelerator on and off as needed. Therefore, the simple fact that Liu discloses adjusting the dose by adjusting the operation of the accelerator does not tell us whether Liu discloses adjusting intensity or irradiation time, or both. Furthermore, even if Liu did specifically disclose adjusting intensity, rather than irradiation time, that would not make it any less obvious to modify Liu to adjust irradiation time instead or in concert.
Applicant argues that Liu can achieve intensity control and therefore achieve neutron dosage control without the need of changing the irradiation time. Examiner agrees. As examiner said, there are three possible ways Liu can achieve the claimed dose control, by adjusting intensity, by adjusting irradiation time, or by doing both. Liu does not specify which they use. Therefore, Liu may adjust intensity only, as applicant suggests. It is also just as possible Liu adjusts irradiation time only, or that Liu does both. All three options are easily imaginable to a person having ordinary skill in the art and all three are equally obvious.
Applicant argues that correcting the actual total dose, as they do, is “clearly different from control of the neutron dose as described in Liu, which involves adjusting/changing the intensity of the neutron beam.” Examiner does not follow the logic. Control of the dose through control of the beam means control of the actual total dose, since the desired total dose can’t be controlled by adjusting the beam. It is clearly the actual total dose that Liu controls. If applicant is suggesting that Liu controls the actual total dose for some purpose other than correcting it to become the desired total dose, what other purpose could Liu have? The very fact that the dose is being controlled implies the dose is being directed to some specific value, and that value, by definition, is the desired total dose.
Conclusion
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 ELIZA W OSENBAUGH-STEWART whose telephone number is (571)270-5782. The examiner can normally be reached 10am - 6pm Pacific Time M-F.
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/ELIZA W OSENBAUGH-STEWART/Primary Examiner, Art Unit 2881
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